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Liu Y, Xu Y, Sun Z, Gao S. Joint association of physical activity and sugar-sweetened beverages with obesity in young U.S. adults: A cross-sectional analysis of NHANES 2007-2020. Prev Med Rep 2025; 53:103043. [PMID: 40235579 PMCID: PMC11999209 DOI: 10.1016/j.pmedr.2025.103043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 03/16/2025] [Accepted: 03/17/2025] [Indexed: 04/17/2025] Open
Abstract
Objective This study aimed to investigate the independent and joint association of sugar-sweetened beverages (SSBs) and physical activity with obesity among young U.S. adults. Methods We selected 11,318 U.S. young adults aged 20-44 years from the National Health and Nutrition Examination Survey (2007-2020). Physical activity was self-reported using the Global Physical Activity Questionnaire, while SSBs consumption was calculated from a single day of twenty-four-hour dietary recall. Multivariable logistic regression models, and sensitivity analyses were used to estimate the associations between SSBs, physical activity, and obesity. Results There were 4216 cases of obesity (35.5 %). A positive relationship between the consumption of SSBs and the prevalence of obesity was observed, while physical activity was negatively associated with the prevalence of obesity. Relative to the moderate SSBs consumption + inactive participants, those who were insufficiently active [adjusted odds ratio (AOR) = 0.75, 95 % CI: 0.58, 0.97] and physically active (AOR = 0.72, 95 % CI: 0.62, 0.85) had a lower likelihood of obesity among moderate SSBs consumers (1-499 kcal/day). However, this pattern was not found in the heavy SSBs consumers (≥ 500 kcal/day) (P > 0.05). Conclusions In conclusion, physical activity was associated with a lower prevalence of obesity among moderate SSBs consumers, while this pattern did not observe in heavy SSBs consumers. Further studies are needed to validate these results and determine causality.
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Affiliation(s)
- Yuhang Liu
- School of Physical Education and Sports, Central China Normal University, Wuhan 430079, PR China
| | - Ying Xu
- Department of Hematology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, PR China
| | - Zhaohong Sun
- College of Physical Education, Chongqing University, Chongqing 401331, PR China
| | - Siyao Gao
- Department of Physical Education, Central South University, Changsha 410083, PR China
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Yu H, Feng N, Zhong W, Han Y, Cheng Y, Zhang Z, Wang Y, Gao P, Huang R, Zhang C, Liu Z, Dong J, He Z, Lai H, Shen Z, Zhai Q. Nmnat2 deficiency in the arcuate nucleus or paraventricular nucleus induces Sarm1-independent neuron loss and liraglutide-reversible obesity. FASEB J 2025; 39:e70400. [PMID: 39964232 DOI: 10.1096/fj.202402546r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 01/08/2025] [Accepted: 02/06/2025] [Indexed: 05/10/2025]
Abstract
Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) plays an important role in maintaining axon integrity, and the arcuate nucleus (ARC), and paraventricular nucleus (PVN) are crucial nuclei in the control of energy balance. However, the effect of Nmnat2 deficiency in ARC and PVN is still unclear. Nmnat2 loxP/loxP or Nmnat2 loxP/loxP , Sarm1 -/- mice were bilaterally injected with AAV-CMV-GFP-Cre once into the ARC, PVN, or lateral parabrachial nucleus (LPBN) to obtain Nmnat2 ARC-/- , Nmnat2 PVN-/- , Nmnat2 LPBN-/- , Nmnat2 ARC-/- , SKO, Nmnat2 PVN-/- , SKO, or Nmnat2 LPBN-/- , SKO mice. Syn1-Cre mice were bilaterally injected with AAV-EF1a-flex-taCasp3-TEVp once into the ARC or PVN to specifically induce neuron loss. Metabolic changes were measured in the mice intraperitoneally injected with or without liraglutide, a glucagon-like peptide-1 (GLP-1) analog. Neuron loss and neuron activation were monitored by immunofluorescence. Deletion of Nmnat2 in ARC or PVN of mice leads to neuron loss, increased food intake, and obesity in a Sarm1-independent manner. Intraperitoneal injection of liraglutide activates neurons in PVN and LPBN, and attenuates hyperphagia and obesity induced by Nmnat2 deletion or apoptosis of Syn1-positive neurons in ARC or PVN, but has no significant effect on neuron loss. Nmnat2 deficiency in LPBN leads to death within 2 weeks, which can be markedly rescued by Sarm1 deficiency. These data show that deletion of Nmnat2 in ARC or PVN in adult mice leads to Sarm1-independent neuron loss, and liraglutide-reversible hyperphagia and obesity. These findings also elucidate the integrated role of ARC or PVN for downregulating food intake, the requirement of LPBN for survival, and the ARC- or PVN-independent effect of GLP-1 on food intake.
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Affiliation(s)
- Huimin Yu
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Ning Feng
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Wuling Zhong
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yumo Han
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
| | - Yalan Cheng
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Zhentong Zhang
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yingqi Wang
- Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Peidong Gao
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Rui Huang
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Cong Zhang
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Zongyang Liu
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Jieya Dong
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Zhishui He
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Hejin Lai
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Ziru Shen
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Qiwei Zhai
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
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Galindo-Padrón AG, Lorenzo-Anota HY, Rueda-Munguía M, García-Carrasco A, Gaitán López M, Vázquez-Garza E, Campos-González E, Lozano O, Cholula-Díaz JL. Study on the Regulated Cell Death of Hypertrophic H9c2 Cells Induced by Au:Ag Nanoparticles. Int J Nanomedicine 2025; 20:1491-1507. [PMID: 39925684 PMCID: PMC11804235 DOI: 10.2147/ijn.s491288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 01/01/2025] [Indexed: 02/11/2025] Open
Abstract
Background and Aim Over the past years, noble metal-based nanoparticles have been extensively investigated for their applications in nanomedicine. However, there are still concerns about the potential adversities that these nanoparticles may present in an organism. In particular, whether they could cause an exacerbated cytotoxic response in susceptible tissues due to damage or disease, such as the heart, liver, spleen, or kidneys. In this regard, this study aims to evaluate the cytotoxicity of mono- and bimetallic nanoparticles of gold and silver (Au:Ag NPs) on healthy and hypertrophic cardiac H9c2 cells, and on healthy and metabolically activated macrophages derived from U937 cells. The main objective of this work is to explore the susceptibility of cells due to exposure to Au:Ag NPs in conditions representing cardiometabolic diseases. Methods Au:Ag NPs were synthesized in different molar ratios (Au:Ag, 100:0, 75:25, 50:50, 25:75, 0:100) using starch as a capping and reducing agent. Their physicochemical properties were characterized through UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Moreover, the effect of the metal-based nanoparticle exposure on healthy and hypertrophic H9c2 cells was measured by analyzing the cellular vitality, the loss of mitochondrial membrane potential (∆Ψm), and the production of mitochondrial reactive oxygen species (mROS). Results The Au:Ag NPs did not affect the cell vitality of healthy or metabolically activated macrophages. On the contrary, healthy H9c2 cells showed decreased mitochondrial metabolism when exposed to NPs with higher Ag concentrations. Furthermore, hypertrophic H9c2 cells were more susceptible to the same NPs compared to their non-hypertrophic counterparts, and presented a pronounced loss of ∆Ψm. In addition, these NPs increased the production of mROS and regulated cell death in both cardiac cells. Conclusion In conclusion, low doses of high-Ag load in Au:Ag NPs produced cytotoxicity on H9c2 cardiac cells, with hypertrophic cells being more susceptible. These results suggest that cardiac hypertrophic conditions are more prone to a cytotoxic response in the presence of bimetallic Au:Ag NPs compared to healthy cells. In addition, this work opens the door to explore the nanotoxicity of noble metal-based NPs in biological disease conditions.
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Affiliation(s)
| | - Helen Yarimet Lorenzo-Anota
- Institute for Obesity Research, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
- School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
| | - Mayte Rueda-Munguía
- Institute for Obesity Research, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
- School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
| | | | - Mabel Gaitán López
- School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
| | - Eduardo Vázquez-Garza
- Institute for Obesity Research, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
| | | | - Omar Lozano
- Institute for Obesity Research, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
- School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
- Cátedra de Cardiología y Medicina Vascular, Tecnologico de Monterrey, Monterrey, Nuevo León, México
| | - Jorge L Cholula-Díaz
- School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico
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Conde KM, Wong H, Fang S, Li Y, Yu M, Deng Y, Liu Q, Fang X, Wang M, Shi Y, Ginnard OZ, Yang Y, Tu L, Liu H, Liu H, Yin N, Bean JC, Han J, Burt ME, Jossy SV, Yang Y, Tong Q, Arenkiel BR, Wang C, He Y, Xu Y. Serotonin neurons integrate GABA and dopamine inputs to regulate meal initiation. Metabolism 2025; 163:156099. [PMID: 39667432 PMCID: PMC11924950 DOI: 10.1016/j.metabol.2024.156099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/04/2024] [Accepted: 12/07/2024] [Indexed: 12/14/2024]
Abstract
Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HTDRN➔arcuate nucleus (ARH) circuit plays a role in meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the role of dopaminergic inputs via dopamine receptor D2 in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, for the initiation of a meal.
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Affiliation(s)
- Kristine M Conde
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - HueyZhong Wong
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Shuzheng Fang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yongxiang Li
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Meng Yu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yue Deng
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Qingzhuo Liu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Xing Fang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Mengjie Wang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yuhan Shi
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Olivia Z Ginnard
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yuxue Yang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Longlong Tu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Hesong Liu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Hailan Liu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Na Yin
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Jonathan C Bean
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Junying Han
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Megan E Burt
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Sanika V Jossy
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yongjie Yang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Qingchun Tong
- Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Benjamin R Arenkiel
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
| | - Chunmei Wang
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yang He
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
| | - Yong Xu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
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Mirzababaei A, Abaj F, Radmehr M, Ghorbani M, Aali Y, Harsini AR, Clark CCT, Mirzaei K. Association of dietary insulin index (DII) and dietary insulin load (DIL) with circadian rhythm and quality of sleep among overweight and obese women: a cross-sectional study. BMC Endocr Disord 2024; 24:277. [PMID: 39716153 DOI: 10.1186/s12902-024-01811-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 12/11/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Obesity is a global issue, with over 1.9 billion adults overweight. Disruption of circadian rhythms (CR) leads to obesity and metabolic disorders. Dietary nutrition significantly impacts sleep disorders and disruption in CR, influencing hormones and inflammation, which can contribute to insomnia. The dietary insulin index (DII) and dietary insulin load (DIL) are important factors in determining sleep quality. The current study aims to investigate the association between DII and DIL with CR and sleep quality among with overweight and obesity women. METHODS A case-control study involved 280 overweight/obese women aged 25-40 from Tehran University Medical Science. They were assessed for dietary intake, physical activity, and sleep using validated questionnaires. The study also assessed body composition, bioelectrical impedance analysis, biochemical components, anthropometric components, and blood pressure. Socio-demographic and lifestyle characteristics, such as age, educational level, physical activity, and smoking habits, were also assessed through questionnaires. RESULT In the crude and adjustment models, high adherence of DII compared with lower adherence increased the odds of poor sleep quality index among participants. This significant association remained even after adjustment for confounding variables (P < 0.05), such that the odds of poor sleep quality index was 1.92 times higher. CONCLUSION This study showed high adherence to DII and DIL may cause CR disruption. Furthermore, higher adherence to DII lead to poor sleep quality in women.
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Affiliation(s)
- Atieh Mirzababaei
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Abaj
- Department of Nutrition, Dietetics, and Food, Monash University, Melbourne, Australia
| | - Mina Radmehr
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Moloud Ghorbani
- Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yasaman Aali
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Asma Rajabi Harsini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, CV1 5FB, UK
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
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Chamas L, Seugnet I, Tanvé O, Enderlin V, Clerget-Froidevaux MS. The Downregulation of the Liver Lipid Metabolism Induced by Hypothyroidism in Male Mice: Metabolic Flexibility Favors Compensatory Mechanisms in White Adipose Tissue. Int J Mol Sci 2024; 25:10792. [PMID: 39409121 PMCID: PMC11477049 DOI: 10.3390/ijms251910792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/03/2024] [Accepted: 09/10/2024] [Indexed: 10/20/2024] Open
Abstract
In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor (Mc4r) and leptin receptor (LepR) expression in the hypothyroid WSB/EiJ mice strain, which reflects their adaptability to maintain their body weight, in contrast to C57BL/6J mice. Thus, this study showed that WSB/EiJ male mice displayed a resistance to the metabolic dysregulations induced by hypothyroidism through compensatory mechanisms. This highlights the importance of metabolic flexibility in the ability to adapt to disturbed circulating TH levels.
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Affiliation(s)
- Lamis Chamas
- CNRS/MNHN UMR 7221 “Physiologie Moléculaire et Adaptation” Phyma, Department of “Life Adaptations” Muséum National d’Histoire Naturelle 57, Rue Cuvier CP 32, 75231 Paris, CEDEX 05, France
| | - Isabelle Seugnet
- CNRS/MNHN UMR 7221 “Physiologie Moléculaire et Adaptation” Phyma, Department of “Life Adaptations” Muséum National d’Histoire Naturelle 57, Rue Cuvier CP 32, 75231 Paris, CEDEX 05, France
| | - Odessa Tanvé
- CNRS/MNHN UMR 7221 “Physiologie Moléculaire et Adaptation” Phyma, Department of “Life Adaptations” Muséum National d’Histoire Naturelle 57, Rue Cuvier CP 32, 75231 Paris, CEDEX 05, France
| | - Valérie Enderlin
- Paris-Saclay Institute of Neuroscience (Neuro-PSI), CNRS UMR 9197, Université Paris-Saclay, 91400 Saclay, France;
| | - Marie-Stéphanie Clerget-Froidevaux
- CNRS/MNHN UMR 7221 “Physiologie Moléculaire et Adaptation” Phyma, Department of “Life Adaptations” Muséum National d’Histoire Naturelle 57, Rue Cuvier CP 32, 75231 Paris, CEDEX 05, France
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Song Y, Xu T, Chen X, Wang N, Sun Z, Chen J, Xia J, Tian W. Brain structural changes in diabetic retinopathy patients: a combined voxel-based morphometry and surface-based morphometry study. Brain Imaging Behav 2024; 18:1131-1143. [PMID: 39172355 DOI: 10.1007/s11682-024-00905-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2024] [Indexed: 08/23/2024]
Abstract
The aim of this study was to investigate alterations in gray matter structure among individuals diagnosed with diabetic retinopathy (DR). This study included a cohort of 32 diabetic patients with retinopathy (DR group, n = 32) and 38 healthy adults (HC group, n = 38). Both cohorts underwent comprehensive psychological and cognitive assessments alongside structural magnetic resonance imaging. The brain's gray matter volume and morphology were analyzed using voxel-based morphometry (VBM) and surface-based morphometry (SBM). Partial correlation analysis was employed to investigate the associations between differences in gray matter volume (GMV) across diverse brain regions and the outcomes of cognitive psychological tests as well as clinical indicators. The VBM results revealed that, in comparison to the healthy control (HC) group, patients with diabetic retinopathy (DR) exhibited reduced gray matter volume (GMV) in the right fusiform gyrus, inferior frontal gyrus, opercular part, and left hippocampus; conversely, an increase in GMV was observed in the right thalamus. The SBM results indicated cortical thinning in the left caudal anterior cingulate cortex, left superior frontal gyrus, left parahippocampal gyrus, and bilateral lingual gyrus in the DR group. Sulcal depth (SD) exhibited increased values in the bilateral rostral middle frontal gyrus, superior frontal gyrus, frontal pole, left precentral gyrus, postcentral gyrus, lateral orbitofrontal gyrus, and right paracentral gyrus. Local gyrification indices (LGIs) decreased in the left caudal middle frontal gyrus and superior frontal gyrus. The fractal dimension (FD) decreased in the posterior cingulate gyrus and isthmus of the cingulate gyrus. The left hippocampal gray matter volume (GMV) in patients with diabetic retinopathy was negatively correlated with disease duration (r = -0.478, p = 0.008) and self-rating depression scale (SAS) score (r = -0.381, p = 0.038). The structural alterations in specific brain regions of individuals with DR, which may contribute to impairments in cognition, emotion, and behavior, provide valuable insights into the neurobiological basis underlying these dysfunctions.
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Affiliation(s)
- Yaqi Song
- Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, 225300, China
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Tianye Xu
- Graduate School of Dalian Medical University, Dalian, Liaoning, 116044, China
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Xiujuan Chen
- Department of Ophthalmology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Ning Wang
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Zhongru Sun
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Jinhua Chen
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
| | - Jianguo Xia
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China.
| | - Weizhong Tian
- Department of Medical Imaging, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China.
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Travers RL, Trim WV, Motta AC, Betts JA, Thompson D. Calorie restriction-induced leptin reduction and T-lymphocyte activation in blood and adipose tissue in men with overweight and obesity. Int J Obes (Lond) 2024; 48:993-1002. [PMID: 38538853 PMCID: PMC11216992 DOI: 10.1038/s41366-024-01513-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 03/13/2024] [Accepted: 03/15/2024] [Indexed: 07/03/2024]
Abstract
BACKGROUND T-Lymphocyte activation is modulated by the adipokine leptin and serum concentrations of this hormone can be reduced with short-term calorie restriction. The aim of this study was to understand whether leptin per se is important in determining levels of T-lymphocyte activation in humans, by investigating whether the reduction in leptin concentration following calorie restriction is associated with a decrease in T-Lymphocyte activation in blood and adipose tissue. METHODS Twelve men with overweight and obesity (age 35-55 years, waist circumference 95-115 cm) reduced their calorie intake by 50% for 3 consecutive days. Blood and subcutaneous adipose tissue were obtained for isolation of immune cells and cytokine analysis. CD4+ and CD8 + T-Lymphocytes were identified and characterised according to their expression of activation markers CD25 and CD69 by flow cytometry. RESULTS Serum leptin was reduced by (mean ± SEM) 31 ± 16% (p < 0.001) following calorie restriction. The percentage of blood CD4 + CD25 + T-lymphocytes and level of CD25 expression on these lymphocytes were significantly reduced by 8 ± 10% (p = 0.016) and 8 ± 4% (p = 0.058), respectively. After calorie restriction, ex vivo leptin secretion from abdominal subcutaneous adipose tissue explants was not changed, and this corresponded with a lack of change in adipose tissue resident T-Lymphocyte activation. CONCLUSIONS Serum leptin was reduced after calorie restriction and this was temporally associated with a reduction in activation of blood CD4 + CD25 + T-Lymphocytes. In abdominal subcutaneous adipose tissue, however, leptin secretion was unaltered, and there were no observed changes in adipose resident T-Lymphocyte activation.
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Affiliation(s)
- Rebecca L Travers
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, BA2 7AY, UK
| | - William V Trim
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, BA2 7AY, UK
- Department of Systems Biology, Harvard Medical School, Boston, MA, MA02115, USA
| | - Alexandre C Motta
- Unilever Food & Health Research Institute R&D, Vlaardingen, The Netherlands
- IMcoMET BV, Vlaardingen, The Netherlands
| | - James A Betts
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, BA2 7AY, UK
| | - Dylan Thompson
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, BA2 7AY, UK.
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9
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Turner RT, Branscum AJ, Iwaniec UT. Long-duration leptin transgene expression in dorsal vagal complex does not alter bone parameters in female Sprague Dawley rats. Bone Rep 2024; 21:101769. [PMID: 38706522 PMCID: PMC11067478 DOI: 10.1016/j.bonr.2024.101769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/21/2024] [Accepted: 04/23/2024] [Indexed: 05/07/2024] Open
Abstract
The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.
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Affiliation(s)
- Russell T. Turner
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
- Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA
| | - Adam J. Branscum
- Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
| | - Urszula T. Iwaniec
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
- Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA
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10
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Conde KM, Wong H, Fang S, Li Y, Yu M, Deng Y, Liu Q, Fang X, Wang M, Shi Y, Ginnard OZ, Yang Y, Tu L, Liu H, Liu H, Yin N, Bean JC, Han J, Burt ME, Jossy SV, Yang Y, Tong Q, Arenkiel BR, Wang C, He Y, Xu Y. 5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.26.591360. [PMID: 38746314 PMCID: PMC11092489 DOI: 10.1101/2024.04.26.591360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.
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Affiliation(s)
- Kristine M. Conde
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - HueyZhong Wong
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Shuzheng Fang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yongxiang Li
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Meng Yu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yue Deng
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Qingzhuo Liu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Xing Fang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Mengjie Wang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yuhan Shi
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Olivia Z. Ginnard
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yuxue Yang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Longlong Tu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Hesong Liu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Hailan Liu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Na Yin
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Jonathan C. Bean
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Junying Han
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Megan E. Burt
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Sanika V. Jossy
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yongjie Yang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Qingchun Tong
- Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Benjamin R. Arenkiel
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Chunmei Wang
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Yang He
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Yong Xu
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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11
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Zhao M, Zhang D, Wang X, Li H, Sun B, Wu Z, Zhu Y, Cao H. Association between lipid profile in early pregnancy and the risk of congenital heart disease in offspring: a prospective cohort study. Sci Rep 2024; 14:3655. [PMID: 38351050 PMCID: PMC10864369 DOI: 10.1038/s41598-024-53876-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 02/06/2024] [Indexed: 02/16/2024] Open
Abstract
This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a prospective cohort design based on the Fujian Birth Cohort Study in China. We recruited pregnant women at ≤ 14 weeks of gestation between 2019 and 2022, and all participants in this study filled out the questionnaire about periconceptional exposure. Simultaneously, we collected participants' fasting blood samples to measure their lipid profile by automatic biochemical analyzer. The outcome was defined as offspring with CHD. A multivariable logistic regression model was used to calculate adjusted odds ratio (AOR) risk estimates, which indicate the associations between maternal lipid profiles and CHD in offspring. Restricted cubic splines were used to estimate their nonlinear relationship. A total of 21,425 pregnant women with an average gestational age of 11.3 (± 1.40) weeks were included in the analysis. The higher triglyceride (AOR 1.201, 95% CI [1.036, 1.394]), low-density lipoprotein (AOR 1.216, 95% CI [1.048, 1.410]), apolipoprotein B (Apo B) (AOR 2.107, 95% CI [1.179, 3.763]) levels were correlated with increased odds of CHD in offspring, while high-density lipoprotein (OR 0.672, 95% CI [0.490, 0.920]) related with decreased odds of CHD in offspring. The restricted cubic spline suggested a nonlinear relationship between total cholesterol (TC) levels and the risk of CHD in offspring (P = 0.0048), but no significant nonlinear relationships were found in other lipid profile. Apolipoprotein A was not related to the risk of CHD in offspring as either a continuous variable or a hierarchical variable. Elevated lipid profile in early pregnancy levels are associated with an increased risk of CHD in offspring. Additionally, there is a non-linear relationship between TC levels and the risk of CHD in offspring.
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Affiliation(s)
- Minli Zhao
- College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou, 350000, China
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, China
- NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-Human Primate (Fujian Maternity and Child Health Hospital), Fujian Medical University, Fuzhou, 350014, China
| | - Danwei Zhang
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, China
| | - Xinrui Wang
- NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-Human Primate (Fujian Maternity and Child Health Hospital), Fujian Medical University, Fuzhou, 350014, China
| | - Haibo Li
- Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China
| | - Bin Sun
- Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China
| | - Zhengqin Wu
- Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China
| | - Yibing Zhu
- Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China.
| | - Hua Cao
- College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou, 350000, China.
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, China.
- Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China.
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12
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He L, Wu D, Liu J, Li G, Chen C, Karrar E, Ahmed IAM, Zhang L, Li J. Comparison of Lipid Composition between Quasipaa spinosa Oil and Rana catesbeiana Oil and Its Effect on Lipid Accumulation in Caenorhabditis elegans. J Oleo Sci 2024; 73:239-251. [PMID: 38311413 DOI: 10.5650/jos.ess23143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024] Open
Abstract
Frog oil has been recognized for its nutritional and medicinal value. However, there is limited research on the role of frog oil in preventing obesity. In this study, we aimed to investigate the lipid composition of Quasipaa spinosa oil (QSO) and Rana catesbeiana oil (RCO) using lipidomics analysis. We compared the lipid accumulation effects of these two kinds of frog oils and soybean oil (SO) in Caenorhabditis elegans (C. elegans). Additionally, we determined the gene expression related to lipid metabolism and used the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199) for validation experiments. The results showed that the lipid composition of QSO and RCO was significantly different (p < 0.05), and QSO was rich in more polyunsaturated fatty acids (PUFAs). After feeding C. elegans, the lipid accumulation of the QSO group was the lowest among the three dietary oil groups. In addition, compared with RCO and SO, QSO significantly inhibited the production of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). The effects of three kinds of dietary oils on the fatty acid composition of C. elegans were significantly different. Compared with SO and RCO, QSO significantly up-regulated (p < 0.05) the expression of sir-2.1 and ech-1 genes. The results showed that QSO might reduce lipid accumulation through the SIRT1 and nuclear hormone signaling pathways. Such a situation was verified experimentally by the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199). This study proposed a new functional oil, laying the groundwork for developing functional foods from Quasipaa spinosa.
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Affiliation(s)
- Lili He
- College of Ocean Food and Biological Engineering, Jimei University
| | - Daren Wu
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
| | - Jingwen Liu
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
| | - Guiling Li
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
| | - Chaoxiang Chen
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
| | - Emad Karrar
- College of Ocean Food and Biological Engineering, Jimei University
| | - Isam A Mohamed Ahmed
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University
| | - Lingyu Zhang
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
| | - Jian Li
- College of Ocean Food and Biological Engineering, Jimei University
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food
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13
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Chen WH, Shi YC, Huang QY, Chen JM, Wang ZY, Lin S, Shi QY. Potential for NPY receptor-related therapies for polycystic ovary syndrome: an updated review. Hormones (Athens) 2023; 22:441-451. [PMID: 37452264 PMCID: PMC10449684 DOI: 10.1007/s42000-023-00460-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 06/13/2023] [Indexed: 07/18/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a complex endocrine disease that can cause female infertility and bring economic burden to families and to society. The clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, and polycystic ovarian changes, often accompanied by insulin resistance and obesity. Although its pathogenesis is unclear, PCOS involves the abnormal regulation of the hypothalamic-pituitary-ovarian axis and the abnormal activation of GnRH neurons. Neuropeptide Y (NPY) is widely distributed in the arcuate nucleus of the hypothalamus and functions as the physiological integrator of two neuroendocrine systems, one governing feeding and the other controlling reproduction. In recent years, an increasing number of studies have focused on the improvement of the reproductive and metabolic status of PCOS through the therapeutic application of NPY and its receptors. In this review, we summarize the central and peripheral regulation of NPY and its receptors in the development of PCOS and discuss the potential for NPY receptor-related therapies for PCOS.
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Affiliation(s)
- Wei-Hong Chen
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China
| | - Yan-Chuan Shi
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China
- Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia
| | - Qiao-Yi Huang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China
| | - Jia-Ming Chen
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China
| | - Zhi-Yi Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China.
- Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia.
| | - Qi-Yang Shi
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China.
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14
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Zhang XL, Zhang XF, Fang Y, Li ML, Shu R, Gong Y, Luo HY, Tian Y. A possible genetic association between obesity and colon cancer in females. Front Endocrinol (Lausanne) 2023; 14:1189570. [PMID: 37711894 PMCID: PMC10497871 DOI: 10.3389/fendo.2023.1189570] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 08/07/2023] [Indexed: 09/16/2023] Open
Abstract
Object There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms. Methods GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions. Results Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p. Conclusion Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.
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Affiliation(s)
- Xiao-li Zhang
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Xin-feng Zhang
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuan Fang
- Department of Hepatobiliary Transplantation, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Meng-li Li
- Department of Respiratory Medicine, Affiliated Hospital of Yunnan University, Kunming, China
| | - Ruo Shu
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yi Gong
- Basic Medical Sciences, Kunming Medical University, Kunming, China
| | - Hua-you Luo
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yan Tian
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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15
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Shibata M, Ozato N, Tsuda H, Mori K, Kinoshita K, Katashima M, Katsuragi Y, Nakaji S, Maeda H. Mouse Model of Anti-Obesity Effects of Blautia hansenii on Diet-Induced Obesity. Curr Issues Mol Biol 2023; 45:7147-7160. [PMID: 37754236 PMCID: PMC10528399 DOI: 10.3390/cimb45090452] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/16/2023] [Accepted: 08/25/2023] [Indexed: 09/28/2023] Open
Abstract
Reportedly, a relationship exists between intestinal microflora and obesity-related lifestyle diseases. Blautia spp. a major intestinal microbiota, accounts for 3-11% of human intestinal microflora. Epidemiological reports have described that people with more visceral fat have less Blautia hansenii in their intestinal tract irrespective of age or gender. However, the effect of oral administration of heat-sterilized Blautia hansenii on obesity has not been clarified. Therefore, the aim of this study was to evaluate the effects of dietary Blautia hansenii administration on obesity in high-fat-diet-induced obesity in a mouse model. Heat-sterilized cells of Blautia hansenii were used. C57BL/6J mice (normal mice, n = 7) were fed with each experimental diet for nine weeks. Diets for experimentation were: normal-fat (NF) diets, high-fat (HF) diets, and high-fat + Blautia hansenii (HF + Blautia) diets. The HF + Blautia group was administered about 1 × 109 (CFU/mouse/day) of Blautia hansenii. During the periods of experimentation, body weight, food intake, water consumption, and fecal weight were recorded, and glucose tolerance tests were performed. Subsequently, the white adipose tissue (WAT) weight and serum components were measured. Short-chain fatty acid contents in the feces and cecum were analyzed. Furthermore, changes in the intestinal microflora were analyzed using meta-genomics analysis. Results showed that the total weight of WAT in the HF + Blautia group was significantly lower (13.2%) than that of the HF group. Moreover, the HF + Blautia group exhibited better glucose tolerance than the HF group. Productivity of short-chain fatty acids in the intestinal tract was at a significantly (p < 0.05) low level in the HF group; on the other hand, it recovered in the HF + Blautia group. Furthermore, there was a higher ratio of Blautia (p < 0.05) in the intestinal tracts of the HF + Blautia group than in the HF group. These results suggest that Blautia hansenii administration suppresses obesity induced by a high-fat diet.
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Affiliation(s)
- Masaki Shibata
- Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki 036-8561, Japan; (M.S.); (H.T.)
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18 Ueda, Morioka 020-0066, Japan
| | - Naoki Ozato
- Health & Wellness Products Research Laboratories, Kao Corp., 2-1-3 Bunka, Sumida-ku 131-8501, Japan; (N.O.); (K.M.); (K.K.); (M.K.); (Y.K.)
| | - Harutoshi Tsuda
- Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki 036-8561, Japan; (M.S.); (H.T.)
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18 Ueda, Morioka 020-0066, Japan
| | - Kenta Mori
- Health & Wellness Products Research Laboratories, Kao Corp., 2-1-3 Bunka, Sumida-ku 131-8501, Japan; (N.O.); (K.M.); (K.K.); (M.K.); (Y.K.)
| | - Keita Kinoshita
- Health & Wellness Products Research Laboratories, Kao Corp., 2-1-3 Bunka, Sumida-ku 131-8501, Japan; (N.O.); (K.M.); (K.K.); (M.K.); (Y.K.)
| | - Mitsuhiro Katashima
- Health & Wellness Products Research Laboratories, Kao Corp., 2-1-3 Bunka, Sumida-ku 131-8501, Japan; (N.O.); (K.M.); (K.K.); (M.K.); (Y.K.)
| | - Yoshihisa Katsuragi
- Health & Wellness Products Research Laboratories, Kao Corp., 2-1-3 Bunka, Sumida-ku 131-8501, Japan; (N.O.); (K.M.); (K.K.); (M.K.); (Y.K.)
| | - Shigeyuki Nakaji
- Department of Social Medicine, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan;
| | - Hayato Maeda
- Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki 036-8561, Japan; (M.S.); (H.T.)
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18 Ueda, Morioka 020-0066, Japan
- Institute of Regional Innovation, Hirosaki University, 2-1-1 Yanagawa, Aomori 038-0012, Japan
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16
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Yu Q, Yu F, Li Q, Zhang J, Peng Y, Wang X, Li T, Yin N, Sun G, Ouyang H, Chen Y, Mine Y, Tsao R, Zhang H. Anthocyanin-Rich Butterfly Pea Flower Extract Ameliorating Low-Grade Inflammation in a High-Fat-Diet and Lipopolysaccharide-Induced Mouse Model. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:11941-11956. [PMID: 37526116 DOI: 10.1021/acs.jafc.3c02696] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
This study aimed to explore the enhancive effects of butterfly pea flower (BF) extracts on metabolic and immune homeostasis in a low-grade inflammation mouse model. The BF extract was found to contain mainly anthocyanins among other flavonoids. BF supplementation alleviated metabolic endotoxemia by lowering the plasma glucose, lipopolysaccharide (LPS), and tumor necrosis factor-α (TNF-α) levels and restored lipid metabolism and the balance between Treg and Th17 cells, thereby inhibiting the dysfunctional liver and abdominal white adipose tissues. BF extract increased the tight junction protein expression and reduced the expression of proinflammatory cytokines, therefore sustaining the colonic mucosa structure. Furthermore, BF extracts reshaped the gut microbiota structure characterized by significantly promoted SCFA-producing gut microbiota such as Akkermansia and Butyricicoccaceae. Additionally, BF extracts enhanced fecal primary bile acid (BA) levels and modulated bile acid signaling in the liver and ileum to facilitate BA synthesis for the restoration of lipid metabolism. In summary, anthocyanin-enriched BF extracts alleviated the profound negative dietary alterations and helped maintain the metabolic health by modulating the various aspects of the gut microenvironment and enhancing hepatic bile acid synthesis.
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Affiliation(s)
- Qinqin Yu
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Fengyao Yu
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Qiong Li
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Jie Zhang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - You Peng
- Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang 332005, China
| | - Xiaoya Wang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Tao Li
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Ning Yin
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Genlin Sun
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Hui Ouyang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Yuhuan Chen
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Yoshinori Mine
- Department of Food Science, University of Guelph, Guelph, Ontario N1G2W1, Canada
| | - Rong Tsao
- Guelph Food Research and Development Centre, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, Ontario N1G 5C9, Canada
| | - Hua Zhang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
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17
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Conde K, Fang S, Xu Y. Unraveling the serotonin saga: from discovery to weight regulation and beyond - a comprehensive scientific review. Cell Biosci 2023; 13:143. [PMID: 37550777 PMCID: PMC10408233 DOI: 10.1186/s13578-023-01091-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 07/21/2023] [Indexed: 08/09/2023] Open
Abstract
The prevalence of obesity is rapidly increasing worldwide, while the development of effective obesity therapies lags behind. Although new therapeutic targets to alleviate obesity are identified every day, and drug efficacy is improving, adverse side effects and increased health risks remain serious issues facing the weight-loss industry. Serotonin, also known as 5-HT, has been extensively studied in relation to appetite reduction and weight loss. As a result, dozens of upstream and downstream neural targets of 5-HT have been identified, revealing a multitude of neural circuits involved in mediating the anorexigenic effect of 5-HT. Despite the rise and fall of several 5-HT therapeutics in recent decades, the future of 5-HT as a therapeutic target for weight-loss therapy looks promising. This review focuses on the history of serotonin, the state of current central serotonin research, previous serotonergic therapies, and the future of serotonin for treating individuals with obesity.
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Affiliation(s)
- Kristine Conde
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, USA.
| | - Shuzheng Fang
- College of Art and Sciences, Washington University in St. Louis, St. Louis, MO, USA
| | - Yong Xu
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, USA.
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA.
- Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Houston, TX, 77030, USA.
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18
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Shi F, Collins S. Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease. Int J Mol Sci 2023; 24:11497. [PMID: 37511253 PMCID: PMC10380887 DOI: 10.3390/ijms241411497] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
The mechanistic target of rapamycin (mTOR) kinase is a central regulator of cell growth and metabolism. It is the catalytic subunit of two distinct large protein complexes, mTOR complex 1 (mTORC1) and mTORC2. mTOR activity is subjected to tight regulation in response to external nutrition and growth factor stimulation. As an important mechanism of signaling transduction, the 'second messenger' cyclic nucleotides including cAMP and cGMP and their associated cyclic nucleotide-dependent kinases, including protein kinase A (PKA) and protein kinase G (PKG), play essential roles in mediating the intracellular action of a variety of hormones and neurotransmitters. They have also emerged as important regulators of mTOR signaling in various physiological and disease conditions. However, the mechanism by which cAMP and cGMP regulate mTOR activity is not completely understood. In this review, we will summarize the earlier work establishing the ability of cAMP to dampen mTORC1 activation in response to insulin and growth factors and then discuss our recent findings demonstrating the regulation of mTOR signaling by the PKA- and PKG-dependent signaling pathways. This signaling framework represents a new non-canonical regulation of mTOR activity that is independent of AKT and could be a novel mechanism underpinning the action of a variety of G protein-coupled receptors that are linked to the mTOR signaling network. We will further review the implications of these signaling events in the context of cardiometabolic disease, such as obesity, non-alcoholic fatty liver disease, and cardiac remodeling. The metabolic and cardiac phenotypes of mouse models with targeted deletion of Raptor and Rictor, the two essential components for mTORC1 and mTORC2, will be summarized and discussed.
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Affiliation(s)
- Fubiao Shi
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Sheila Collins
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
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19
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Nogueiras R, Nauck MA, Tschöp MH. Gut hormone co-agonists for the treatment of obesity: from bench to bedside. Nat Metab 2023:10.1038/s42255-023-00812-z. [PMID: 37308724 DOI: 10.1038/s42255-023-00812-z] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 04/24/2023] [Indexed: 06/14/2023]
Abstract
The discovery and development of so-called gut hormone co-agonists as a new class of drugs for the treatment of diabetes and obesity is considered a transformative breakthrough in the field. Combining action profiles of multiple gastrointestinal hormones within a single molecule, these novel therapeutics achieve synergistic metabolic benefits. The first such compound, reported in 2009, was based on balanced co-agonism at glucagon and glucagon-like peptide-1 (GLP-1) receptors. Today, several classes of gut hormone co-agonists are in development and advancing through clinical trials, including dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) co-agonists (first described in 2013), and triple GIP-GLP-1-glucagon co-agonists (initially designed in 2015). The GLP-1-GIP co-agonist tirzepatide was approved in 2022 by the US Food and Drug Administration for the treatment of type 2 diabetes, providing superior HbA1c reductions compared to basal insulin or selective GLP-1 receptor agonists. Tirzepatide also achieved unprecedented weight loss of up to 22.5%-similar to results achieved with some types of bariatric surgery-in non-diabetic individuals with obesity. In this Perspective, we summarize the discovery, development, mechanisms of action and clinical efficacy of the different types of gut hormone co-agonists, and discuss potential challenges, limitations and future developments.
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Affiliation(s)
- Ruben Nogueiras
- CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Galicia Agency of Innovation, Xunta de Galicia, Santiago de Compostela, Spain
| | - Michael A Nauck
- Diabetes, Endocrinology and Metabolism Section, Medical Department I, St. Josef-Hospital, Katholisches Klinikum Bochum, Ruhr University of Bochum, Bochum, Germany
| | - Matthias H Tschöp
- Helmholtz Zentrum München, Neuherberg, Germany.
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, München, Germany.
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20
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Xu H, Wang J, Liu Y, Wang Y, Zhong X, Li C, Wang K, Guo X, Xie C. Development of a simultaneous quantification method for the gut microbiota-derived core nutrient metabolome in mice and its application in studying host-microbiota interaction. Anal Chim Acta 2023; 1251:341039. [PMID: 36925303 DOI: 10.1016/j.aca.2023.341039] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/28/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023]
Abstract
The gut microbiota interacts with the host via production of various metabolites of dietary nutrients. Herein, we proposed the concept of the gut microbiota-derived core nutrient metabolome, which covers 43 metabolites in carbohydrate metabolism, glycolysis, tricarboxylic acid cycle and amino acid metabolism, and established a quantitative UPLC-Q/TOF-MS method through 3-nitrophenylhydrazine derivatization to investigate the influence of obesity on the gut microbiota in mice. All metabolites could be simultaneously analyzed via separation on a BEH C18 column within 18 min. The lower limits of quantification of most analytes were less than 1 μM. Validation results demonstrated suitability for the analysis of mouse fecal samples. The method was then applied to detect the gut microbiota-derived nutrient metabolome in the feces of high-fat diet induced obese (DIO) and ob/ob (leptin-deficient) mice, as well as obesity-prone (OP) and obesity-resistant (OR) mice. Compared to the control groups, there were 13, 23 and 10 differentially abundant metabolites detected in ob/ob, DIO and OP groups, respectively. Among them, amino acids including leucine, isoleucine, glycine, methionine, tyrosine and glutamine were co-downregulated in the obese or OP mice and exhibited inverse association with body weight. 16S rDNA analysis revealed that the genera Lactobacillus and Dubosiella were also inversely associated with body weight and positively correlated with fecal amino acids. Collectively, our work provides an effective and simplified method for simultaneous quantifying the gut microbiota-derived core nutrient metabolome in mouse feces, which could assist various future studies on host-microbiota metabolic interaction.
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Affiliation(s)
- Hualing Xu
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Jiawen Wang
- Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 2022241, PR China.
| | - Yameng Liu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Yangyang Wang
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China; State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, PR China.
| | - Xianchun Zhong
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Cuina Li
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Kanglong Wang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Xiaozhen Guo
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
| | - Cen Xie
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.
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21
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Li H, Xu Y, Jiang Y, Jiang Z, Otiz-Guzman J, Morrill JC, Cai J, Mao Z, Xu Y, Arenkiel BR, Huang C, Tong Q. The melanocortin action is biased toward protection from weight loss in mice. Nat Commun 2023; 14:2200. [PMID: 37069175 PMCID: PMC10110624 DOI: 10.1038/s41467-023-37912-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 04/05/2023] [Indexed: 04/19/2023] Open
Abstract
The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. Furthermore, gain of function of the melanocortin action through overexpression of MC4R, POMC or its derived peptides had little effect on obesity prevention or reversal. These results reveal a bias of the melanocortin action towards protection of weight loss and provide a neural basis behind the well-known, but mechanistically ill-defined, predisposition to obesity development.
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Affiliation(s)
- Hongli Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Yuanzhong Xu
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Yanyan Jiang
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Zhiying Jiang
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Joshua Otiz-Guzman
- Department of Molecular and Human Genetics and Department of Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA
| | - Jessie C Morrill
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, 77030, Houston, TX, USA
| | - Jing Cai
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, 77030, Houston, TX, USA
| | - Zhengmei Mao
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Yong Xu
- Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA
| | - Benjamin R Arenkiel
- Department of Molecular and Human Genetics and Department of Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA
| | - Cheng Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
| | - Qingchun Tong
- Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
- MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, 77030, Houston, TX, USA.
- Department of Neurobiology and Anatomy of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
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22
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Wang X, Wu B, Sun G, Gao J, Huang T, Liu J, Zhou Q, He X, Zhang S, Wang CY, Zhang Z, Zhu H. Dietary selenomethionine attenuates obesity by enhancing beiging process in white adipose tissue. J Nutr Biochem 2023; 113:109230. [PMID: 36435293 DOI: 10.1016/j.jnutbio.2022.109230] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 09/21/2022] [Accepted: 10/05/2022] [Indexed: 11/25/2022]
Abstract
Imbalanced nutrient intake causes abnormal energy metabolism, which results in obesity. There is feasible evidence that selenium-rich (Se-rich) foods may alleviate obesity and enhance general public health, but the underlying mechanisms remain elusive. Herein we examined the effect of Se supplementation on white adipose tissue beiging process. The mice were fed with a normal diet or a Se-deficient high-fat diet (DHFD) until significant differences in terms of body weight, glucose tolerance and insulin sensitivity. Next, mice in the DHFD group were changed to a high-fat diet (HFD) containing specified amounts of selenomethionine (SeMet) (0, 150, 300, and 600 μg/kg) and continued to feed for 14 weeks. Notably, 150 μg/kg SeMet supplement highly protected mice from DHFD-induced obesity, insulin resistance, and lipid deposits in the liver and kidney, and featured by the enhanced beiging process in white adipose tissue and increased energy expenditure. Moreover, upon cold challenge, 150 μg/kg SeMet supplement enhanced cold tolerance in mice by inducing adipose beiging to promote energy expenditure, as evidenced by the increased expression of uncoupling protein-1 (UCP1) in adipocytes. Similarly, SeMet (10 μM) promoted the differentiation of beige adipocytes from the stromal vascular fraction. Collectively, our data support that optimal supplementation of SeMet could enhance the beiging process to attenuate HFD-induced obesity, which provides new insights into the relationship between dietary SeMet and type 2 diabetes.
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Affiliation(s)
- Xiaohui Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Bo Wu
- The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, China
| | - Guogen Sun
- Hubei Selenium and Human Health Institute, Enshi, Hubei, China
| | - Jia Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Teng Huang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Jing Liu
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Qing Zhou
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Xiaoyu He
- Branch of National Clinical Research Center for Metabolic Diseases, Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shu Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Cong-Yi Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
| | - Zixiong Zhang
- The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, China.
| | - He Zhu
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China.
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23
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Song Z, Liu N, He Y, Chen J, Li J, Wang F, Wu Z. Knockout of ICAT in Adipose Tissue Alleviates Fibro-inflammation in Obese Mice. Inflammation 2023; 46:404-417. [PMID: 36181623 DOI: 10.1007/s10753-022-01742-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/08/2022] [Accepted: 09/14/2022] [Indexed: 11/24/2022]
Abstract
The E2 promoter binding factor 1 (E2F1) and the Wnt/β-catenin signaling are crucial in regulating metabolic homeostasis including obesity. The β-catenin interacting protein 1 (CTNNBIP1), also known as the inhibitor of β-catenin and TCF4 (ICAT), is required for E2F1 to inhibit the activity of β-catenin. However, the role of ICAT in E2F1 regulating obesity-related metabolic disorders remains unknown. In the present study, male adipose tissue-specific ICAT knockout (ICATadi-/-) C57BL/6 J mice and control littermates aged 6-8 weeks were fed with high-fat diet (HFD) for 12 weeks to explore the effect of ICAT on lipid metabolism and obesity-related disorders. Results showed that the adipose tissue-specific ICAT knockout had negligible effect on lipid metabolism, reflected by no difference in body weight, fat mass, and the expression of proteins involved in lipid metabolism in white adipose tissue (WAT) and the liver between the ICATadi-/- mice and the control littermate (ICATfl/fl) mice. However, the knockout of ICAT reduced inflammatory response in WAT and the liver. Additionally, Sirius red staining results showed that deletion of ICAT attenuated fibrosis and reduced mRNA levels of transforming growth factor β1(TGF-β1), matrix metallopeptidase 2 (Mmp2), Mmp3, and collagen, type V, alpha 1 (Col5a1) in WAT and the liver. These results suggested that knockout of ICAT improved the metabolic abnormalities of obese mice through attenuating adipose tissue and the liver inflammation as well as fibrosis. Our findings may provide a new insight to understand the role of ICAT in inflammation and fibrosis.
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Affiliation(s)
- Zhuan Song
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China
| | - Ning Liu
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China
| | - Yu He
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China
| | - Jingqing Chen
- Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, 100193, China
| | - Jun Li
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China
| | - Fengchao Wang
- National Institute of Biological Sciences (NIBS), Beijing, 102206, China
| | - Zhenlong Wu
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China. .,Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China.
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24
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Teixeira GP, Guimarães KC, Soares AGNS, Marqueze EC, Moreno CRC, Mota MC, Crispim CA. Role of chronotype in dietary intake, meal timing, and obesity: a systematic review. Nutr Rev 2022; 81:75-90. [PMID: 35771674 DOI: 10.1093/nutrit/nuac044] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
CONTEXT Recent studies show that dietary habits and obesity seem to be influenced by chronotype, which reflects an individual's preference for the timing of sleeping, eating, and activity in a 24-hour period. OBJECTIVE This review aimed to analyze the association of chronotype with dietary habits, namely energy and macronutrient intakes, meal timing, and eating patterns, as well as with obesity. DATA SOURCES PubMed/MEDLINE, LILACS, and Google Scholar databases were searched between 2004 and 2020. Study selection was performed by 2 authors independently; disagreements on eligibility of articles were resolved by a third author. After assessment of 12 060 abstracts, 43 studies (21 articles on obesity; 13 on food consumption, meal timing, and eating patterns; and 9 that addressed both obesity and dietary behavior) were included. DATA EXTRACTION A standard form was used to extract study design, country, number of participants, method of chronotype determination, and main findings. DATA ANALYSIS Approximately 95% of included studies showed an association between eveningness and at least 1 unhealthy eating habit. Morningness was associated with regular consumption of fresh and minimally processed foods. In addition, about 47% of studies showed a higher association between late types and obesity. CONCLUSION Late types are more likely to present unhealthy eating habits, such as eating late at night, skipping breakfast often, and eating processed/ultraprocessed foods, while early types are more likely to have healthy and protective habits, such as eating early and eating predominantly fresh/minimally processed foods. Intermediate types tend to have a pattern of health and eating more similar to early types than to late types. Late types are also more likely to present higher weight and body mass index than early or intermediate types. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42021256078.
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Affiliation(s)
- Gabriela P Teixeira
- are with the Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Kisian C Guimarães
- are with the Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Ana Gabriela N S Soares
- are with the Nutrition Course, Faculty of Medicine, Federal University of Uberlândia, Minas Gerais Uberlândia, Brazil
| | - Elaine C Marqueze
- are with the School of Public Health, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Cláudia R C Moreno
- are with the School of Public Health, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Maria C Mota
- are with the Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Cibele A Crispim
- are with the Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.,are with the Nutrition Course, Faculty of Medicine, Federal University of Uberlândia, Minas Gerais Uberlândia, Brazil
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Cepharanthine action in preventing obesity and hyperlipidemia in rats on a high-fat high sucrose diet. Saudi Pharm J 2022; 30:1683-1690. [PMID: 36601507 PMCID: PMC9805974 DOI: 10.1016/j.jsps.2022.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 09/15/2022] [Indexed: 01/07/2023] Open
Abstract
Background It was demonstrated that cepharanthine (CEP), derived from Stephania cepharantha hayata, is a potent inhibitor of the ABCC10 transmembrane protein. It is approved to be a natural product or remedy. The present study focuses on investigating whether cepharanthine effectively reduces hyperlipidemia and obesity in an experimental hyperlipidemic rat model. Method Four groups of Wistar rats were assigned randomly to the following groups: a high-fat high sucrose diet (HFHS), normal-fat diet (NFD), HFHS plus cepraranthine (10 mg/kg) (HFHS-C), and a HFHS diet with atorvastatin (HFHS-A). The responses of rats were observed on the basis of serum and hepatic biochemical parameters, food intake, and body weight after CEP treatment, and assessing the histopathological modifications by the optical microscope in the liver and its cells. Results Significant improvement in the serum total cholesterol (TC), serum triglycerides (TG), and serum low-density lipoprotein (LDL) levels were observed following CEP treatment. We have also observed significant improvement in the structure of liver tissue and reduced-fat droplets in the cytoplasm. Moreover, CEP had a significant effect in preventing the gain in body weight of animals, and food intake was not significantly affected. Conclusion Our research results revealed that CEP significantly improved dyslipidemia and prevented the accumulation of fatty deposits in the rats' liver tissue fed an HFHS diet. In addition, CEP exerted an anti-obesity effect.
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Shobatake R, Ota H, Takahashi N, Ueno S, Sugie K, Takasawa S. The Impact of Intermittent Hypoxia on Metabolism and Cognition. Int J Mol Sci 2022; 23:12957. [PMID: 36361741 PMCID: PMC9654766 DOI: 10.3390/ijms232112957] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/15/2022] [Accepted: 10/23/2022] [Indexed: 11/29/2022] Open
Abstract
Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that result in oxidative stress and systemic inflammation. Since SAS is epidemiologically strongly correlated with type 2 diabetes/insulin resistance, obesity, hypertension, and dyslipidemia included in metabolic syndrome, the effects of IH on gene expression in the corresponding cells of each organ have been studied intensively to clarify the molecular mechanism of the association between SAS and metabolic syndrome. Dementia has recently been recognized as a serious health problem due to its increasing incidence, and a large body of evidence has shown its strong correlation with SAS and metabolic disorders. In this narrative review, we first outline the effects of IH on the expression of genes related to metabolism in neuronal cells, pancreatic β cells, hepatocytes, adipocytes, myocytes, and renal cells (mainly based on the results of our experiments). Next, we discuss the literature regarding the mechanisms by which metabolic disorders and IH develop dementia to understand how IH directly and indirectly leads to the development of dementia.
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Affiliation(s)
- Ryogo Shobatake
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
- Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan
- Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan
| | - Hiroyo Ota
- Department Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Nobuyuki Takahashi
- Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan
| | - Satoshi Ueno
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Kazuma Sugie
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Shin Takasawa
- Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan
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Dynamic Resistance Exercise Alters Blood ApoA-I Levels, Inflammatory Markers, and Metabolic Syndrome Markers in Elderly Women. Healthcare (Basel) 2022; 10:healthcare10101982. [PMID: 36292427 PMCID: PMC9601716 DOI: 10.3390/healthcare10101982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 10/04/2022] [Accepted: 10/06/2022] [Indexed: 11/04/2022] Open
Abstract
Combined endurance and dynamic-resistance exercise has important anti-inflammatory effects, altering vascular endothelial function, and helping to prevent and treat aging-related metabolic syndrome (MS). We studied changes in 40 elderly women aged ≥ 65 years (control group (no MS), n = 20, mean age: 68.23 ± 2.56 years; MS group, n = 19, mean age: 71.42 ± 5.87 years; one left). The exercise program comprised dynamic-resistance training using elastic bands, three times weekly, for six months. We analyzed body composition, blood pressure, physical fitness, and MS-related blood variables including ApoA-I, antioxidant factors, and inflammatory markers. After the program, the MS group showed significant reductions in waist-hip ratio, waist circumference, diastolic blood pressure, blood insulin, and HOMA-IR, and a significant increase in HSP70 (p < 0.05). Both groups showed significant increases in ApoA-I levels, ApoA-I/HDL-C ratio, SOD2, IL-4, and IL-5 levels (p < 0.05). Active-resistance training-induced changes in ApoA-I were significantly positively correlated with changes in HDL-C and HSP70, and significantly negatively correlated with changes in triglycerides, C-reactive protein, and TNF-α (p < 0.05). Active-resistance training qualitatively altered HDL, mostly by altering ApoA-I levels, relieving vascular inflammation, and improving antioxidant function. This provides evidence that dynamic-resistance exercise can improve physical fitness and MS risk factors in elderly women.
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Proteomic analysis of the effect of high-fat-diet and voluntary physical activity on mouse liver. PLoS One 2022; 17:e0273049. [PMID: 35981048 PMCID: PMC9387828 DOI: 10.1371/journal.pone.0273049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 08/01/2022] [Indexed: 11/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NALFD), characterized by an abnormal accumulation of triglycerides in hepatocytes, is closely linked to insulin resistance, metabolic syndrome, and changes in lipogenesis in the liver. The accumulation of hepatic lipids can lead to a range of pathologies from mild steatosis to severe cirrhosis. Endurance exercise is known to ameliorate the adverse health effects of NAFLD. Therefore, we aimed to investigate the effect of voluntary wheel running (VWR) on the metabolic changes in the livers of high-fat diet (HFD)-induced NAFLD mice and used LC-MS/MS (Liquid chromatography–mass spectrometry) to determine whether the tested intervention affected the protein expression profiles of the mouse livers. Male C57BL/6 mice were randomly divided into three groups: control (CON), high-fat diet sedentary group (HFD), high-fat diet VWR group (HFX). HFX group performed voluntary wheel running into individually cages, given a high-fat diet for 12 weeks. Food consumption, body weight, and running distance were measured every week. Using 2D (2-dimensional)-gel electrophoresis, we detected and quantitatively analyzed the protein expression with >2.0-fold change in the livers of HFD-fed mice, HFD-fed exercise (HFX) mice, and chow-fed mice. Body weight was significantly increased in HFD compared to CON (P < 0.05). The 2D-gel electrophoresis analysis indicated that there was a difference between CON and HFD groups, showing 31 increased and 27 decreased spots in the total 302 paired spots in the HFD group compared to CON. The analysis showed 43 increased and 17 decreased spots in the total 258 spots in the HFX group compared to CON. Moreover, 12 weeks of VWR showed an increase of 35 and a decrease of 8 spots in a total of 264 paired spots between HFD and HFX. LC-MS/MS of HFD group revealed that proteins involved in ketogenesis, lipid metabolism, and the metabolism of drugs and xenobiotics were upregulated, whereas detoxifying proteins, mitochondrial precursors, transport proteins, proteasomes, and proteins involved in amino acid metabolism were downregulated. On the other hand, VWR counteracted the protein expression profile of HFD-fed mice by upregulating molecular chaperones, gluconeogenesis-, detoxification-, proteasome-, and energy metabolism-related proteins. This study provided a molecular understanding of the HFD- and exercise-induced protein marker expression and presented the beneficial effects of exercise during pathophysiological conditions.
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Morari J, Haddad-Tóvolli R, Silva Nogueira PA, Teixeira CJ, Maróstica R, Tobar N, Ramos CD, Velloso LA, Dias Bobbo VC, Anhê GF. Body mass variability in age-matched outbred male Swiss mice is associated to differential control of food intake by ghrelin. Mol Cell Endocrinol 2022; 550:111646. [PMID: 35413387 DOI: 10.1016/j.mce.2022.111646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 04/05/2022] [Accepted: 04/07/2022] [Indexed: 11/23/2022]
Abstract
Swiss mice belong to an outbred strain of mice largely used as a model for experimental obesity induced by high fat diet (HFD). We have previously demonstrated that a given cohort of age-matched Swiss mice is hallmarked by heterogeneous changes in body weight when exposed to HFD. The reasons underlying such variability, however, are not completely understood. Therefore we aimed to clarify the mechanisms underlying the variability in spontaneous weight gain in age-matched male swiss mice. To achieve that, individuals in a cohort of age-matched male Swiss mice were categorized as prone to body mass gain (PBMG) and resistant to body mass gain (RBMG). PBMG animals had higher caloric intake and body mass gain. RBMG and PBMG mice had a similar reduction in food intake when challenged with leptin but only RBMG exhibited a drop in ghrelin concentrations after refeeding. PBMG also showed increased midbrain levels of ghrelin receptor (Ghsr) and Dopamine receptor d2 (Drd2) mRNAs upon refeeding. Pharmacological blockade of GHSR with JMV3002 failed to reduce food intake in PMBG mice as it did in RBMG. On the other hand, the response to JMV3002 seen in PBMG was hallmarked by singular transcriptional response in the midbrain characterized by a simultaneous increase in both tyrosine hydroxylase (Th) and Proopiomelanocortin (Pomc) expressions. In conclusion, our data show that differences in the expression of genes related to the reward system in the midbrain as well as in ghrelin concentrations in serum correlate with spontaneous variability in body mass and food intake seen in age-matched male Swiss mice.
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Affiliation(s)
- Joseane Morari
- Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, 13083-887, Brazil; Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil; Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, 13083-881, Brazil.
| | - Roberta Haddad-Tóvolli
- Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil
| | - Pedro Augusto Silva Nogueira
- Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil
| | - Caio Jordão Teixeira
- Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524. Prof. Lineu Prestes Ave., ICB1, Sao Paulo, SP, 05508-000, Brazil
| | - Rafael Maróstica
- Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil
| | - Natália Tobar
- Department of Radiology, University of Campinas, Campinas, Sao Paulo, 13084-970, Brazil
| | - Celso Dario Ramos
- Department of Radiology, University of Campinas, Campinas, Sao Paulo, 13084-970, Brazil
| | - Licio Augusto Velloso
- Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, 13083-887, Brazil; Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil
| | - Vanessa Cristina Dias Bobbo
- Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas, Campinas, Sao Paulo, 13083-864, Brazil
| | - Gabriel Forato Anhê
- Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, 13083-881, Brazil
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Liu T, Xu Y, Yi CX, Tong Q, Cai D. The hypothalamus for whole-body physiology: from metabolism to aging. Protein Cell 2022; 13:394-421. [PMID: 33826123 PMCID: PMC9095790 DOI: 10.1007/s13238-021-00834-x] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 03/01/2021] [Indexed: 01/05/2023] Open
Abstract
Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.
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Affiliation(s)
- Tiemin Liu
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Institute of Metabolism and Integrative Biology, Human Phenome Institute, and Collaborative Innovation Center for Genetics and Development, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, 200438 China
| | - Yong Xu
- grid.39382.330000 0001 2160 926XChildren’s Nutrition Research Center, Department of Pediatrics, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA
| | - Chun-Xia Yi
- grid.7177.60000000084992262Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam Gastroenterology Endocrinology Metabolism, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, Netherlands
| | - Qingchun Tong
- grid.453726.10000 0004 5906 7293Brown Foundation Institute of Molecular Medicine, Department of Neurobiology and Anatomy, University of Texas McGovern Medical School, Graduate Program in Neuroscience of MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030 USA
| | - Dongsheng Cai
- grid.251993.50000000121791997Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 USA
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Rodents on a high-fat diet born to mothers with gestational diabetes exhibit sex-specific lipidomic changes in reproductive organs. Acta Biochim Biophys Sin (Shanghai) 2022; 54:736-747. [PMID: 35643955 PMCID: PMC9828243 DOI: 10.3724/abbs.2022052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Maternal gestatonal diabetes mellitus (GDM) and offspring high-fat diet (HFD) have been shown to have sex-specific detrimental effects on the health of the offspring. Maternal GDM combined with an offspring HFD alters the lipidomic profiles of offspring reproductive organs with sex hormones and increases insulin signaling, resulting in offspring obesity and diabetes. The pre-pregnancy maternal GDM mice model is established by feeding maternal C57BL/6 mice and their offspring are fed with either a HFD or a low-fat diet (LFD). Testis, ovary and liver are collected from offspring at 20 weeks of age. The lipidomic profiles of the testis and ovary are characterized using gas chromatography-mass spectrometry. Male offspring following a HFD have elevated body weight. In reproductive organs and hormones, male offspring from GDM mothers have decreased testes weights and testosterone levels, while female offspring from GDM mothers show increased ovary weights and estrogen levels. Maternal GDM aggravates the effects of an offspring HFD in male offspring on the AKT pathway, while increasing the risk of developing inflammation when expose to a HFD in female offspring liver. Testes are prone to the effect of maternal GDM, whereas ovarian metabolite profiles are upregulated in maternal GDM and downregulated in offspring following an HFD. Maternal GDM and an offspring HFD have different metabolic effects on offspring reproductive organs, and PUFAs may protect against detrimental outcomes in the offspring, such as obesity and diabetes.
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Maternal lipid profile in pregnancy and embryonic size: a population-based prospective cohort study. BMC Pregnancy Childbirth 2022; 22:333. [PMID: 35436866 PMCID: PMC9016996 DOI: 10.1186/s12884-022-04647-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 03/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background Lipids are crucial for fetal growth and development. Maternal lipid concentrations are associated with fetal growth in the second and third trimester of pregnancy and with birth outcomes. However, it is unknown if this association starts early in pregnancy or arises later during fetal development. The aim of this study was to investigate the association between the maternal lipid profile in early pregnancy and embryonic size. Methods We included 1474 women from the Generation R Study, a population based prospective birth cohort. Both embryonic size and the maternal lipid profile were measured between 10 weeks + 1 day and 13 weeks + 6 days gestational age. The maternal lipid profile was defined as total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), remnant cholesterol, non-high-density (non-HDL-c) lipoprotein cholesterol concentrations and the triglycerides/high-density lipoprotein (TG/HDL-c) ratio. Additionally, maternal glucose concentrations were assessed. Embryonic size was assessed using crown-rump length (CRL) measurements. Associations were studied with linear regression models, adjusted for confounding factors: maternal age, pre-pregnancy body mass index (BMI), parity, educational level, ethnicity, smoking and folic acid supplement use. Results Triglycerides and remnant cholesterol concentrations are positively associated with embryonic size (fully adjusted models, 0.17 SDS CRL: 95% CI 0.03; 0.30, and 0.17 SDS: 95% CI 0.04; 0.31 per 1 MoM increase, respectively). These associations were not present in women with normal weight (triglycerides and remnant cholesterol: fully adjusted model, 0.44 SDS: 95% CI 0.15; 0.72). Associations between maternal lipid concentrations and embryonic size were not attenuated after adjustment for glucose concentrations. Total cholesterol, HDL-c, LDL-c, non-HDL-c concentrations and the TG/HDL-c ratio were not associated with embryonic size. Conclusions Higher triglycerides and remnant cholesterol concentrations in early pregnancy are associated with increased embryonic size, most notably in overweight women. Trial registration The study protocol has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre (Erasmus MC), Rotterdam (MEC-2007-413). Written informed consent was obtained from all participants. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-04647-6.
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Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal 2022; 36:e24420. [PMID: 35421277 PMCID: PMC9102524 DOI: 10.1002/jcla.24420] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/19/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune‐neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut–brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms. Materials and methods Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies. Results The gut–brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus–pituitary–adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity. Conclusion This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.
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Affiliation(s)
- Arezoo Asadi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Negar Shadab Mehr
- Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | | | - Fazlollah Shokri
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.,Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
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Sbierski-Kind J, Grenkowitz S, Schlickeiser S, Sandforth A, Friedrich M, Kunkel D, Glauben R, Brachs S, Mai K, Thürmer A, Radonić A, Drechsel O, Turnbaugh PJ, Bisanz JE, Volk HD, Spranger J, von Schwartzenberg RJ. Effects of caloric restriction on the gut microbiome are linked with immune senescence. MICROBIOME 2022; 10:57. [PMID: 35379337 PMCID: PMC8978410 DOI: 10.1186/s40168-022-01249-4] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 02/07/2022] [Indexed: 05/05/2023]
Abstract
BACKGROUND Caloric restriction can delay the development of metabolic diseases ranging from insulin resistance to type 2 diabetes and is linked to both changes in the composition and metabolic function of the gut microbiota and immunological consequences. However, the interaction between dietary intake, the microbiome, and the immune system remains poorly described. RESULTS We transplanted the gut microbiota from an obese female before (AdLib) and after (CalRes) an 8-week very-low-calorie diet (800 kcal/day) into germ-free mice. We used 16S rRNA sequencing to evaluate taxa with differential abundance between the AdLib- and CalRes-microbiota recipients and single-cell multidimensional mass cytometry to define immune signatures in murine colon, liver, and spleen. Recipients of the CalRes sample exhibited overall higher alpha diversity and restructuring of the gut microbiota with decreased abundance of several microbial taxa (e.g., Clostridium ramosum, Hungatella hathewayi, Alistipi obesi). Transplantation of CalRes-microbiota into mice decreased their body fat accumulation and improved glucose tolerance compared to AdLib-microbiota recipients. Finally, the CalRes-associated microbiota reduced the levels of intestinal effector memory CD8+ T cells, intestinal memory B cells, and hepatic effector memory CD4+ and CD8+ T cells. CONCLUSION Caloric restriction shapes the gut microbiome which can improve metabolic health and may induce a shift towards the naïve T and B cell compartment and, thus, delay immune senescence. Understanding the role of the gut microbiome as mediator of beneficial effects of low calorie diets on inflammation and metabolism may enhance the development of new therapeutic treatment options for metabolic diseases. TRIAL REGISTRATION NCT01105143 , "Effects of negative energy balance on muscle mass regulation," registered 16 April 2010. Video Abstract.
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Affiliation(s)
- Julia Sbierski-Kind
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Sophia Grenkowitz
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
| | - Stephan Schlickeiser
- BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin and Berlin Institute of Health (BIH), Berlin, Germany
| | - Arvid Sandforth
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Marie Friedrich
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
| | - Désirée Kunkel
- Berlin Institute of Health (BIH), Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Flow & Mass Cytometry Core Facility, Berlin, Germany
| | - Rainer Glauben
- Medical Department for Gastroenterology, Infectious Diseases and Rheumatology, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sebastian Brachs
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
| | - Knut Mai
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
| | | | | | | | - Peter J Turnbaugh
- Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA
| | - Jordan E Bisanz
- Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA
- Department for Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
| | - Hans-Dieter Volk
- Berlin Institute of Health (BIH), Berlin, Germany
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Joachim Spranger
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany.
- Berlin Institute of Health (BIH), Berlin, Germany.
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
| | - Reiner Jumpertz von Schwartzenberg
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Chariteplatz 1, 10117, Berlin, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
- Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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Sot J, García-Arribas AB, Abad B, Arranz S, Portune K, Andrade F, Martín-Nieto A, Velasco O, Arana E, Tueros I, Ferreri C, Gaztambide S, Goñi FM, Castaño L, Alonso A. Erythrocyte Membrane Nanomechanical Rigidity Is Decreased in Obese Patients. Int J Mol Sci 2022; 23:ijms23031920. [PMID: 35163842 PMCID: PMC8836476 DOI: 10.3390/ijms23031920] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/04/2022] [Accepted: 02/06/2022] [Indexed: 12/13/2022] Open
Abstract
This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar–nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.
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Affiliation(s)
- Jesús Sot
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Aritz B. García-Arribas
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Beatriz Abad
- SGIKER, Servicios Generales de Investigación (SGiker), Universidad del País Vasco, 48940 Leioa, Spain;
| | - Sara Arranz
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Kevin Portune
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Fernando Andrade
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Alicia Martín-Nieto
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Olaia Velasco
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Eunate Arana
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Itziar Tueros
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Carla Ferreri
- ISOF, Consiglio Nazionale delle Ricerche, Via Piero Gobetti, 101, 40129 Bologna, Italy;
| | - Sonia Gaztambide
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Félix M. Goñi
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Luis Castaño
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Alicia Alonso
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
- Correspondence:
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Different Changes in Adipokines, Lipid Profile, and TNF-Alpha Levels between 10 and 20 Whole Body Cryostimulation Sessions in Individuals with I and II Degrees of Obesity. Biomedicines 2022; 10:biomedicines10020269. [PMID: 35203477 PMCID: PMC8869184 DOI: 10.3390/biomedicines10020269] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/16/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023] Open
Abstract
Obesity is associated with chronic inflammation. While cold therapy influences the pro/antioxidative status of an individual, by affecting adipokine levels and the lipid profile, the effect of body mass index (BMI) on the response to cold exposure is unclear. We analyzed the link between BMI and the differences in effects of whole-body stimulation, depending on the number of treatments, on specific physiological parameters in men. Twenty-seven non-active men were divided into three groups: N (n = 9, BMI < 24.9), IOb (n = 9, BMI 30.0–34.9), and IIOb (BMI ≥ 35.0). The subjects participated in 20 3-min cryochamber sessions (−120 °C), 1/day, 5 days/week. Body composition was analyzed before and after treatment. Blood adiponectin (ADP), leptin (LEP), and tumor necrosis factor alpha (TNF-alpha) levels, and the lipid profile were analyzed three times: at baseline and up to 2 h after 10 and 20 sessions. The 20 treatments caused significant changes in body composition. Between 10 and 20 whole-body cryostimulation (WBC) sessions, a significant decreased was observed in the LEP and TNF-alpha levels. No significant changes in the lipid profile were noted. However, a positive tendency to regain the metabolic balance in adipose tissue was apparent in the IOb group in the tested period (decreased TG levels, increased HDL levels or the HDL/LDL ratio, and significantly decreased visceral adiposity index levels). Collectively, for people with obesity increasing the number of treatments above the standard 10 should be recommended.
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Agarwal S, Singh V, Chauhan K. Antidiabetic potential of seaweed and their bioactive compounds: a review of developments in last decade. Crit Rev Food Sci Nutr 2022; 63:5739-5770. [PMID: 35048763 DOI: 10.1080/10408398.2021.2024130] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diabetes Mellitus is a public health problem worldwide due to high morbidity and mortality rate associated with it. Diabetes can be managed by synthetic hypoglycemic drugs, although their persistent uses have several side effects. Hence, there is a paradigm shift toward the use of natural products having antidiabetic potential. Seaweeds, large marine benthic algae, are an affluent source of various bioactive compounds, including phytochemicals and antioxidants thus exhibiting various health promoting properties. Seaweed extracts and its bioactive compounds have antidiabetic potential as they inhibit carbohydrate hydrolyzing enzymes in vitro and exhibit blood glucose lowering effect in random and post prandial blood glucose tests in vivo. In addition, they have been associated with reduced weight gain in animals probably by decreasing mRNA expression of pro-inflammatory cytokines with concomitant increase in mRNA expression levels of anti-inflammatory cytokines. Their beneficial effect has been seen in serum and hepatic lipid profile and antioxidant enzymes indicating the protective role of seaweeds against free radicals mediated oxidative stress induced hyperglycemia and associated hyperlipidemia. However, the detailed and in-depth studies of seaweeds as whole, their bioactive isolates and their extracts need to be explored further for their health benefits and wide application in food, nutraceutical and pharmaceutical industries.
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Affiliation(s)
- Surbhi Agarwal
- Department of Food Science and Technology, National Institute of Food Technology Entrepreneurship and Management, Sonipet, India
| | - Vikas Singh
- Department of Food Business Management and Entrepreneurship Development, National Institute of Food Technology Entrepreneurship and Management, Kundli, India
| | - Komal Chauhan
- Department of Food Science and Technology, National Institute of Food Technology Entrepreneurship and Management, Sonipet, India
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Jiang L, Yilmaz M, Uehara M, Cavazzoni CB, Kasinath V, Zhao J, Naini SM, Li X, Banouni N, Fiorina P, Shin SR, Tullius SG, Bromberg JS, Sage PT, Abdi R. Characterization of Leptin Receptor + Stromal Cells in Lymph Node. Front Immunol 2022; 12:730438. [PMID: 35111151 PMCID: PMC8801441 DOI: 10.3389/fimmu.2021.730438] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 12/29/2021] [Indexed: 11/14/2022] Open
Abstract
Lymph node (LN)-resident stromal cells play an essential role in the proper functioning of LNs. The stromal compartment of the LN undergoes significant compensatory changes to produce a milieu amenable for regulation of the immune response. We have identified a distinct population of leptin receptor-expressing (LepR+) stromal cells, located in the vicinity of the high endothelial venules (HEVs) and lymphatics. These LepR+ stromal cells expressed markers for fibroblastic reticular cells (FRCs), but they lacked markers for follicular dendritic cells (FDCs) and marginal reticular cells (MRCs). Leptin signaling deficiency led to heightened inflammatory responses within the LNs of db/db mice, leakiness of HEVs, and lymphatic fragmentation. Leptin signaling through the JAK/STAT pathway supported LN stromal cell survival and promoted the anti-inflammatory properties of these cells. Conditional knockout of the LepR+ stromal cells in LNs resulted in HEV and extracellular matrix (ECM) abnormalities. Treatment of ob/ob mice with an agonist leptin fusion protein restored the microarchitecture of LNs, reduced intra-LN inflammatory responses, and corrected metabolic abnormalities. Future studies are needed to study the importance of LN stomal cell dysfunction to the pathogenesis of inflammatory responses in type 2 diabetes (T2D) in humans.
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Affiliation(s)
- Liwei Jiang
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Mine Yilmaz
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Mayuko Uehara
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Cecilia B. Cavazzoni
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Vivek Kasinath
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Jing Zhao
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Said Movahedi Naini
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Xiaofei Li
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Naima Banouni
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Paolo Fiorina
- Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Su Ryon Shin
- Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, United States
| | - Stefan G. Tullius
- Division of Transplant Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Jonathan S. Bromberg
- Departments of Surgery and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Peter T. Sage
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Reza Abdi
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
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Dinda B, Dinda M. Natural Products, a Potential Source of New Drugs Discovery to Combat Obesity and Diabetes: Their Efficacy and Multi-targets Actions in Treatment of These Diseases. NATURAL PRODUCTS IN OBESITY AND DIABETES 2022:101-275. [DOI: 10.1007/978-3-030-92196-5_4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Shobatake R, Ota H, Takahashi N, Ueno S, Sugie K, Takasawa S. Anorexigenic Effects of Intermittent Hypoxia on the Gut-Brain Axis in Sleep Apnea Syndrome. Int J Mol Sci 2021; 23:364. [PMID: 35008784 PMCID: PMC8745445 DOI: 10.3390/ijms23010364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 02/07/2023] Open
Abstract
Sleep apnea syndrome (SAS) is a breathing disorder characterized by recurrent episodes of upper-airway collapse, resulting in intermittent hypoxia (IH) during sleep. Experimental studies with animals and cellular models have indicated that IH leads to attenuation of glucose-induced insulin secretion from pancreatic β cells and to enhancement of insulin resistance in peripheral tissues and cells, such as the liver (hepatocytes), adipose tissue (adipocytes), and skeletal muscles (myocytes), both of which could lead to obesity. Although obesity is widely recognized as a major factor in SAS, it is controversial whether the development of SAS could contribute directly to obesity, and the effect of IH on the expression of appetite regulatory genes remains elusive. Appetite is regulated appropriately by both the hypothalamus and the gut as a gut-brain axis driven by differential neural and hormonal signals. In this review, we summarized the recent epidemiological findings on the relationship between SAS and feeding behavior and focused on the anorexigenic effects of IH on the gut-brain axis by the IH-induced up-regulation of proopiomelanocortin and cocaine- and amphetamine-regulated transcript in neuronal cells and the IH-induced up-regulation of peptide YY, glucagon-like peptide-1 and neurotensin in enteroendocrine cells and their molecular mechanisms.
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Affiliation(s)
- Ryogo Shobatake
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan; (S.U.); (K.S.)
- Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan;
- Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan;
| | - Hiroyo Ota
- Department Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan;
| | - Nobuyuki Takahashi
- Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan;
| | - Satoshi Ueno
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan; (S.U.); (K.S.)
| | - Kazuma Sugie
- Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan; (S.U.); (K.S.)
| | - Shin Takasawa
- Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan;
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Tokarek J, Gadzinowska J, Młynarska E, Franczyk B, Rysz J. What Is the Role of Gut Microbiota in Obesity Prevalence? A Few Words about Gut Microbiota and Its Association with Obesity and Related Diseases. Microorganisms 2021; 10:microorganisms10010052. [PMID: 35056501 PMCID: PMC8777962 DOI: 10.3390/microorganisms10010052] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/22/2021] [Accepted: 12/26/2021] [Indexed: 01/09/2023] Open
Abstract
Obesity is becoming the most dangerous lifestyle disease of our time, and its effects are already being observed in both developed and developing countries. The aim of this study was to investigate the impact of gut microbiota on the prevalence of obesity and associated morbidities, taking into consideration underlying molecular mechanisms. In addition to exploring the relationship between obesity and fecal microorganisms with their metabolites, the study also focused on the factors that would be able to stimulate growth and remodeling of microbiota. Assessed articles were carefully classified according to a predetermined criterion and were critically appraised and used as a basis for conclusions. The considered articles and reviews acknowledge that intestinal microbiota forms a multifunctional system that might significantly affect human homeostasis. It has been proved that alterations in the gut microbiota are found in obese and metabolically diseased patients. The imbalance of microbiome composition, such as changes in Bacteroidetes/Firmicutes ratio and presence of different species of genus Lactobacillus, might promote obesity and comorbidities (type 2 diabetes mellitus, hypertension, dyslipidemia, depression, obstructive sleep apnea). However, there are also studies that contradict this theory. Therefore, further well-designed studies are needed to improve the knowledge about the influence of microbiota, its metabolites, and probiotics on obesity.
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Annie-Mathew AS, Prem-Santhosh S, Jayasuriya R, Ganesh G, Ramkumar KM, Sarada DVL. The pivotal role of Nrf2 activators in adipocyte biology. Pharmacol Res 2021; 173:105853. [PMID: 34455076 DOI: 10.1016/j.phrs.2021.105853] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 01/07/2023]
Abstract
Adipose tissue is instrumental in maintaining metabolic homeostasis by regulating energy storage in the form of triglycerides. In the case of over-nutrition, adipocytes favorably regulate lipogenesis over lipolysis and accumulate excess triglycerides, resulting in increased adipose tissue mass. An abnormal increase in hypertrophic adipocytes is associated with chronic complications such as insulin resistance, obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Experimental studies indicate the occurrence of oxidative stress in the pathogenesis of obesity. A common underlying link between increasing adipose tissue mass and oxidative stress is the Nuclear Factor Erythroid 2-related factor 2 (Nrf2), Keap1-Nrf2-ARE signaling, which plays an indispensable role in metabolic homeostasis by regulating oxidative and inflammatory responses. Additionally, Nrf2 also activates CCAAT/enhancer-binding protein α, (C/EBP-α), C/EBP-β and peroxisome proliferator-activated receptor γ (PPARγ) the crucial pro-adipogenic factors that promote de novo adipogenesis. Hence, at the forefront of research is the quest for prospecting novel compounds to modulate Nrf2 activity in the context of adipogenesis and obesity. This review summarizes the molecular mechanism behind the activation of the Keap1-Nrf2-ARE signaling network and the role of Nrf2 activators in adipocyte pathophysiology.
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Affiliation(s)
- A S Annie-Mathew
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Subramanian Prem-Santhosh
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Ravichandran Jayasuriya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India; SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Goutham Ganesh
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India; SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India; SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
| | - D V L Sarada
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
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Nogueiras R. MECHANISMS IN ENDOCRINOLOGY: The gut-brain axis: regulating energy balance independent of food intake. Eur J Endocrinol 2021; 185:R75-R91. [PMID: 34260412 PMCID: PMC8345901 DOI: 10.1530/eje-21-0277] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 07/14/2021] [Indexed: 12/15/2022]
Abstract
Obesity is a global pandemic with a large health and economic burden worldwide. Bodyweight is regulated by the ability of the CNS, and especially the hypothalamus, to orchestrate the function of peripheral organs that play a key role in metabolism. Gut hormones play a fundamental role in the regulation of energy balance, as they modulate not only feeding behavior but also energy expenditure and nutrient partitioning. This review examines the recent discoveries about hormones produced in the stomach and gut, which have been reported to regulate food intake and energy expenditure in preclinical models. Some of these hormones act on the hypothalamus to modulate thermogenesis and adiposity in a food intake-independent fashion. Finally, the association of these gut hormones to eating, energy expenditure, and weight loss after bariatric surgery in humans is discussed.
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Affiliation(s)
- Ruben Nogueiras
- Department of Physiology, CIMUS, USC, CIBER Fisiopatología Obesidad y Nutrición (CiberOBN), Instituto Salud Carlos III, Galician Agency of Innovation, Xunta de Galicia, Santiago de Compostela, Spain
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Coating beef tallow with calcium soap improves dietary pellet quality and promotes an effective diet-induced obese mouse model. Anim Feed Sci Technol 2021. [DOI: 10.1016/j.anifeedsci.2021.115008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Li J, Rajput A, Kosoy D, Umekawa S, Rajput A, Chang J, Patel V. Rapid orbital lipolysis associated with critical illness and colectomy. Radiol Case Rep 2021; 16:2347-2350. [PMID: 34306279 PMCID: PMC8258791 DOI: 10.1016/j.radcr.2021.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/02/2021] [Accepted: 06/02/2021] [Indexed: 11/18/2022] Open
Abstract
Orbital lipolysis typically develops in the setting of a chronic catabolic state. The acute development and rapid progression of orbital lipolysis are much less commonly described. In this report, we present a rare case of a 64-year-old male who progressed from normal orbital fat content to marked orbital lipolysis in less than one month following episodes of undifferentiated shock, colonic perforation, and total colectomy. We outline the clinical course, describe the characteristic imaging findings, and provide a review of the cellular mechanisms underlying lipolysis. Our case suggests that multiple concurrent illnesses can combine to produce an extreme metabolic demand that may contribute to the uncommon development of rapidly-progressing orbital lipolysis.
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Affiliation(s)
- Joy Li
- University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
| | - Aikta Rajput
- St. George's University, University Centre, Grenada
| | - David Kosoy
- St. George's University, University Centre, Grenada
| | - Sari Umekawa
- The Queen's Medical Center, Department of Pulmonary Critical Care, Honolulu, HI, USA
| | - Anuj Rajput
- Los Angeles Imaging and Interventional Consultants at PIH Health, Department of Radiology, Whittier, CA, USA
| | - Jessica Chang
- University of Southern California, Keck School of Medicine, Department of Ophthalmology, Los Angeles, CA, USA
| | - Vishal Patel
- University of Southern California, Keck School of Medicine, Department of Radiology, Los Angeles, CA, USA
- Corresponding author.
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Jiménez-Cortegana C, García-Galey A, Tami M, del Pino P, Carmona I, López S, Alba G, Sánchez-Margalet V. Role of Leptin in Non-Alcoholic Fatty Liver Disease. Biomedicines 2021; 9:biomedicines9070762. [PMID: 34209386 PMCID: PMC8301314 DOI: 10.3390/biomedicines9070762] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/14/2021] [Accepted: 06/17/2021] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, in addition to excessive calorie intake compared to energy expenditure, affecting both adults and children. The increase in the number of cases, together with the higher morbimortality that this disease entails with respect to the general population, makes NAFLD a serious public health problem. Closely related to the development of this disease, there is a hormone derived from adipocytes, leptin, which is involved in energy homeostasis and lipid metabolism. Numerous studies have verified the relationship between persistent hyperleptinemia and the development of steatosis, fibrinogenesis and liver carcinogenesis. Therefore, further studies of the role of leptin in the NAFLD spectrum could represent an advance in the management of this set of diseases.
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Affiliation(s)
- Carlos Jiménez-Cortegana
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
| | - Alba García-Galey
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
| | - Malika Tami
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
| | - Pilar del Pino
- Unit of Digestive Diseases, Virgen Macarena University Hospital, 41073 Seville, Spain; (P.d.P.); (I.C.)
| | - Isabel Carmona
- Unit of Digestive Diseases, Virgen Macarena University Hospital, 41073 Seville, Spain; (P.d.P.); (I.C.)
| | - Soledad López
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
| | - Gonzalo Alba
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
| | - Víctor Sánchez-Margalet
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain; (C.J.-C.); (A.G.-G.); (M.T.); (S.L.); (G.A.)
- Correspondence:
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Eibl G, Rozengurt E. Metformin: review of epidemiology and mechanisms of action in pancreatic cancer. Cancer Metastasis Rev 2021; 40:865-878. [PMID: 34142285 DOI: 10.1007/s10555-021-09977-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 05/27/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic ductal adenocarcinoma continues to be a lethal disease, for which efficient treatment options are very limited. Increasing efforts have been taken to understand how to prevent or intercept this disease at an early stage. There is convincing evidence from epidemiologic and preclinical studies that the antidiabetic drug metformin possesses beneficial effects in pancreatic cancer, including reducing the risk of developing the disease and improving survival in patients with early-stage disease. This review will summarize the current literature about the epidemiological data on metformin and pancreatic cancer as well as describe the preclinical evidence illustrating the anticancer effects of metformin in pancreatic cancer. Underlying mechanisms and targets of metformin will also be discussed. These include direct effects on transformed pancreatic epithelial cells and indirect, systemic effects on extra-pancreatic tissues.
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Affiliation(s)
- Guido Eibl
- Department of Surgery, David Geffen School of Medicine At UCLA, Los Angeles, CA, USA.
| | - Enrique Rozengurt
- Department of Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, USA
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Andersson B, Tan EP, McGreal SR, Apte U, Hanover JA, Slawson C, Lagerlöf O. O-GlcNAc cycling mediates energy balance by regulating caloric memory. Appetite 2021; 165:105320. [PMID: 34029673 DOI: 10.1016/j.appet.2021.105320] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/26/2022]
Abstract
Caloric need has long been thought a major driver of appetite. However, it is unclear whether caloric need regulates appetite in environments offered by many societies today where there is no shortage of food. Here we observed that wildtype mice with free access to food did not match calorie intake to calorie expenditure. While the size of a meal affected subsequent intake, there was no compensation for earlier under- or over-consumption. To test how spontaneous eating is subject to caloric control, we manipulated O-linked β-N-acetylglucosamine (O-GlcNAc), an energy signal inside cells dependent on nutrient access and metabolic hormones. Genetic and pharmacological manipulation in mice increasing or decreasing O-GlcNAcylation regulated daily intake by controlling meal size. Meal size was affected at least in part due to faster eating speed. Without affecting meal frequency, O-GlcNAc disrupted the effect of caloric consumption on future intake. Across days, energy balance was improved upon increased O-GlcNAc levels and impaired upon removal of O-GlcNAcylation. Rather than affecting a perceived need for calories, O-GlcNAc regulates how a meal affects future intake, suggesting that O-GlcNAc mediates a caloric memory and subsequently energy balance.
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Affiliation(s)
- Björn Andersson
- Department of Pediatric Surgery, Uppsala University Hospital, 75185, Uppsala, Sweden
| | - Ee Phie Tan
- Sanford Burnham Prebys Medical Discovery Institute, 92037, CA, USA
| | - Steven R McGreal
- Department of Pharmacology, Toxicology and Therapeutics, Kansas University, 66160, KS, USA
| | - Udayan Apte
- Department of Pharmacology, Toxicology and Therapeutics, Kansas University, 66160, KS, USA
| | - John A Hanover
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, 20892, MD, USA
| | - Chad Slawson
- Department of Biochemistry and Molecular Biology, Kansas University, 66160, KS, USA
| | - Olof Lagerlöf
- Department of Clinical Sciences, Umeå University, 901 87, Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, 901 87, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, 901 87, Umeå, Sweden.
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Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice. Int J Mol Sci 2021; 22:ijms22105390. [PMID: 34065474 PMCID: PMC8161011 DOI: 10.3390/ijms22105390] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 11/17/2022] Open
Abstract
Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.
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50
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Chan CC, Harley ITW, Pfluger PT, Trompette A, Stankiewicz TE, Allen JL, Moreno-Fernandez ME, Damen MSMA, Oates JR, Alarcon PC, Doll JR, Flick MJ, Flick LM, Sanchez-Gurmaches J, Mukherjee R, Karns R, Helmrath M, Inge TH, Weisberg SP, Pamp SJ, Relman DA, Seeley RJ, Tschöp MH, Karp CL, Divanovic S. A BAFF/APRIL axis regulates obesogenic diet-driven weight gain. Nat Commun 2021; 12:2911. [PMID: 34006859 PMCID: PMC8131685 DOI: 10.1038/s41467-021-23084-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 04/12/2021] [Indexed: 02/07/2023] Open
Abstract
The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcutaneous white adipocytes unveils upregulation of lipid metabolism pathways, with BAFF inducing white adipose tissue (WAT) lipolysis. Brown adipose tissue (BAT) from BAFF-overexpressing mice exhibits increased Ucp1 expression and BAFF promotes brown adipocyte respiration and in vivo energy expenditure. A proliferation-inducing ligand (APRIL), a BAFF homolog, similarly modulates WAT and BAT lipid handling. Genetic deletion of both BAFF and APRIL augments diet-induced obesity. Lastly, BAFF/APRIL effects are conserved in human adipocytes and higher BAFF/APRIL levels correlate with greater BMI decrease after bariatric surgery. Together, the BAFF/APRIL axis is a multifaceted immune regulator of weight gain and adipose tissue function.
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Affiliation(s)
- Calvin C Chan
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Isaac T W Harley
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Division of Rheumatology, Department of Internal Medicine and Department of Immunology & Microbiology, The University of Colorado Denver, Aurora, CO, USA
| | - Paul T Pfluger
- Research Unit NeuroBiology of Diabetes, Helmholtz Center Munich, Neuherberg, Germany
- Institute for Diabetes and Obesity, Helmholtz Center Munich, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Metabolic Diseases, Technische Universität München, Munich, Germany
| | - Aurelien Trompette
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- University of Lausanne, Service de Pneumologie, CHUV, CLED 02.206, Epalinges, Switzerland
| | - Traci E Stankiewicz
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jessica L Allen
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- , Charlotte, NC, USA
| | - Maria E Moreno-Fernandez
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Michelle S M A Damen
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jarren R Oates
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Pablo C Alarcon
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jessica R Doll
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Matthew J Flick
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Leah M Flick
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- , Chapel Hill, NC, USA
| | - Joan Sanchez-Gurmaches
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Rajib Mukherjee
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Rebekah Karns
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Michael Helmrath
- Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Stem Cell & Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Thomas H Inge
- Department of Surgery, Children's Hospital Colorado, Aurora, CO, USA
| | | | - Sünje J Pamp
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - David A Relman
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Randy J Seeley
- Department of Surgery, Internal Medicine and Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA
| | - Matthias H Tschöp
- Institute for Diabetes and Obesity, Helmholtz Center Munich, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Metabolic Diseases, Technische Universität München, Munich, Germany
| | - Christopher L Karp
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Global Health Discovery & Translational Sciences, Bill & Melinda Gates Foundation, Seattle, WA, USA
| | - Senad Divanovic
- Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA.
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
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