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Kulkarni H, Gaikwad AB. The mitochondria-gut microbiota crosstalk - A novel frontier in cardiovascular diseases. Eur J Pharmacol 2025; 998:177562. [PMID: 40157703 DOI: 10.1016/j.ejphar.2025.177562] [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] [Received: 02/12/2025] [Revised: 03/06/2025] [Accepted: 03/26/2025] [Indexed: 04/01/2025]
Abstract
Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and cardiomyopathy among others, remain the leading cause of global morbidity and mortality. Despite advances in treatment, the complex pathophysiology of CVDs necessitates innovative approaches to improve patient outcomes. Recent research has uncovered a dynamic interplay between mitochondria and gut microbiota, fundamentally altering our understanding of cardiovascular health. However, while existing studies have primarily focused on individual components of this axis, this review examines the bidirectional communication between these biological systems and their collective impact on cardiovascular health. Mitochondria, serving as cellular powerhouses, are crucial for maintaining cardiovascular homeostasis through oxidative phosphorylation (OXPHOS), calcium regulation, and redox balance. Simultaneously, the gut microbiota influences cardiovascular function through metabolite production, barrier integrity maintenance, and immune system modulation. The mitochondria-gut microbiota axis operates through various molecular mechanisms, including microbial metabolites such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFA), and secondary bile acids, which directly influence mitochondrial function. Conversely, mitochondrial stress signals and damage-associated molecular patterns (DAMPs) affect gut microbial communities and barrier function. Key signalling pathways, including AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the silent information regulator 1-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1-PGC-1α) axis, integrate these interactions, highlighting their role in CVD pathogenesis. Understanding these interactions has revealed promising therapeutic targets, suggesting new therapies aimed at both mitochondrial function and gut microbiota composition. Thus, this review provides a comprehensive framework for leveraging the mitochondria-gut microbiota axis in providing newer therapeutics for CVDs by targeting the AMPK/SIRT-1/PGC-1α/NF-κB signalling.
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Affiliation(s)
- Hrushikesh Kulkarni
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India
| | - Anil Bhanudas Gaikwad
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India.
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Hosseini FS, Behrouzi A, Shafaie E, Sharifi F, Ejtahed HS. Assessment of gut microbiota in the elderly with sarcopenic obesity: a case-control study. J Diabetes Metab Disord 2025; 24:83. [PMID: 40093788 PMCID: PMC11909374 DOI: 10.1007/s40200-025-01584-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/04/2025] [Indexed: 03/19/2025]
Abstract
Objectives Sarcopenic obesity is a multifactorial disorder commonly found in elderly individuals. One contributing factor is gut microbiota dysbiosis. This study compared the abundance of certain bacteria in elderly individuals with obesity and sarcopenic obesity. Methods The study included 50 elderly individuals over 65 with a body mass index (BMI) of over 30 kg/m², both sexes. Participants were divided into two groups, each with 25 individuals, based on the diagnosis of sarcopenia using the EWGSOP2 criteria. Individuals with underlying diseases, those using antibiotics, and those with a history of gastrointestinal surgery were excluded. Stool samples were stored at -80 °C, and DNA was extracted using standard kits. Bacterial DNA sample quality was assessed using a Nanodrop device. Bacterial frequency was measured using qPCR. The log cfu for each bacteria was calculated and compared in both groups using an independent t-test. Spearman measured the correlation between bacterial genera and physical performance in SPSS 26. Results The case group had a significantly higher average age (70.96) than the control group (68.32). The average BMI was the same in both groups. The frequency of Escherichia (p-value = 0.046) and Bifidobacterium (p-value = 0.017) was significantly higher in the case group. There was no significant difference in the frequency of Lactobacillus and Akkermansia. Conclusion The study uncovered substantial differences in gut microbiota composition between elderly individuals experiencing sarcopenic obesity and those with obesity alone. The findings suggest that dysbiosis, characterized by an excessive presence of Bifidobacterium, Escherichia, and Akkermansia, may be associated with sarcopenic obesity. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-025-01584-x.
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Affiliation(s)
| | - Ava Behrouzi
- Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
| | - Ebrahim Shafaie
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Farshad Sharifi
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Cheong LYT, Saipuljumri EN, Loi GWZ, Zeng J, Lo CH. Autolysosomal Dysfunction in Obesity-induced Metabolic Inflammation and Related Disorders. Curr Obes Rep 2025; 14:43. [PMID: 40366502 PMCID: PMC12078456 DOI: 10.1007/s13679-025-00638-8] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/05/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE OF REVIEW Obesity is a global health crisis affecting individuals across all age groups, significantly increasing the risk of metabolic disorders such as type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), and cardiovascular diseases. The World Health Organization reported in 2022 that 2.5 billion adults were overweight, with 890 million classified as obese, emphasizing the urgent need for effective interventions. A critical aspect of obesity's pathophysiology is meta-inflammation-a chronic, systemic low-grade inflammatory state driven by excess adipose tissue, which disrupts metabolic homeostasis. This review examines the role of autolysosomal dysfunction in obesity-related metabolic disorders, exploring its impact across multiple metabolic organs and evaluating potential therapeutic strategies that target autophagy and lysosomal function. RECENT FINDINGS Emerging research highlights the importance of autophagy in maintaining cellular homeostasis and metabolic balance. Obesity-induced lysosomal dysfunction impairs the autophagic degradation process, contributing to the accumulation of damaged organelles and toxic aggregates, exacerbating insulin resistance, lipotoxicity, and chronic inflammation. Studies have identified autophagic defects in key metabolic tissues, including adipose tissue, skeletal muscle, liver, pancreas, kidney, heart, and brain, linking autophagy dysregulation to the progression of metabolic diseases. Preclinical investigations suggest that pharmacological and nutritional interventions-such as AMPK activation, caloric restriction mimetics, and lysosomal-targeting compounds-can restore autophagic function and improve metabolic outcomes in obesity models. Autolysosomal dysfunction is a pivotal contributor to obesity-associated metabolic disorders , influencing systemic inflammation and metabolic dysfunction. Restoring autophagy and lysosomal function holds promise as a therapeutic strategy to mitigate obesity-driven pathologies. Future research should focus on translating these findings into clinical applications, optimizing targeted interventions to improve metabolic health and reduce obesity-associated complications.
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Affiliation(s)
- Lenny Yi Tong Cheong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore
| | | | - Gavin Wen Zhao Loi
- School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia
| | - Jialiu Zeng
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, 13244, USA.
- Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY, 13244, USA.
| | - Chih Hung Lo
- Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY, 13244, USA.
- Department of Biology, Syracuse University, Syracuse, NY, 13244, USA.
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Lin D, Rezaei MJ. Plant polysaccharides and antioxidant benefits for exercise performance and gut health: from molecular pathways to clinic. Mol Cell Biochem 2025; 480:2827-2846. [PMID: 39692997 DOI: 10.1007/s11010-024-05178-8] [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] [Received: 09/24/2024] [Accepted: 11/26/2024] [Indexed: 12/19/2024]
Abstract
In the last three decades, our understanding of how exercise induces oxidative stress has significantly advanced. Plant polysaccharides, such as dietary fibers and resistant starches, have been shown to enhance exercise performance by improving energy metabolism, reducing fatigue, increasing strength and stamina, mitigating oxidative stress post-exercise, facilitating muscle recovery, and aiding in detoxification. Moreover, antioxidants found in plant-based foods play a crucial role in protecting the body against oxidative stress induced by intense physical activity. By scavenging free radicals and reducing oxidative damage, antioxidants can improve exercise endurance, enhance recovery, and support immune function. Furthermore, the interaction between plant polysaccharides and antioxidants in the gut microbiota can lead to synergistic effects on overall health and performance. This review provides a comprehensive overview of the current research on plant polysaccharides and antioxidants in relation to exercise performance and gut health.
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Affiliation(s)
- Di Lin
- School of Sports, Zhengzhou Shengda University, Zhengzhou, 451191, Henan, China.
| | - Mohammad J Rezaei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Mo X, Cheng R, Shen L, Sun Y, Wang P, Jiang G, Wen L, Li X, Peng X, Liao Y, He R, Yan H, Liu L. High-fat diet induces sarcopenic obesity in natural aging rats through the gut-trimethylamine N-oxide-muscle axis. J Adv Res 2025; 70:405-422. [PMID: 38744403 PMCID: PMC11976414 DOI: 10.1016/j.jare.2024.05.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024] Open
Abstract
INTRODUCTION The lack of suitable animal models for sarcopenic obesity (SO) limits in-depth research into the disease. Emerging studies have demonstrated that gut dysbiosis is involved in the development of SO. As the importance of microbial metabolites is starting to unveil, it is necessary to comprehend the specific metabolites associated with gut microbiota and SO. OBJECTIVES We aimed to investigate whether high-fat diet (HFD) causes SO in natural aging animal models and specific microbial metabolites that are involved in linking HFD and SO. METHODS Young rats received HFD or control diet for 80 weeks, and obesity-related metabolic disorders and sarcopenia were measured. 16S rRNA sequencing and non-targeted and targeted metabolomics methods were used to detect fecal gut microbiota and serum metabolites. Gut barrier function was evaluated by intestinal barrier integrity and intestinal permeability. Trimethylamine N-oxide (TMAO) treatment was further conducted for verification. RESULTS HFD resulted in body weight gain, dyslipidemia, impaired glucose tolerance, insulin resistance, and systemic inflammation in natural aging rats. HFD also caused decreases in muscle mass, strength, function, and fiber cross-sectional area and increase in muscle fatty infiltration in natural aging rats. 16S rRNA sequencing and nontargeted and targeted metabolomics analysis indicated that HFD contributed to gut dysbiosis, mainly characterized by increases in deleterious bacteria and TMAO. HFD destroyed intestinal barrier integrity and increased intestinal permeability, as evaluated by reducing levels of colonic mucin-2, tight junction proteins, goblet cells and elevating serum level of fluorescein isothiocyanate-dextran 4. Correlation analysis showed a positive association between TMAO and SO. In addition, TMAO treatment aggravated the development of SO in HFD-fed aged rats through regulating the ROS-AKT/mTOR signaling pathway. CONCLUSION HFD leads to SO in natural aging rats, partially through the gut-microbiota-TMAO-muscle axis.
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Affiliation(s)
- Xiaoxing Mo
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Ruijie Cheng
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Lihui Shen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Yunhong Sun
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Pei Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Guanhua Jiang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Lin Wen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Xiaoqin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Xiaobo Peng
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Yuxiao Liao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
| | - Ruikun He
- CAS Engineering Laboratory for Nutrition, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
| | - Hong Yan
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
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Liu Z, Peng H, Liu P, Duan F, Yang Y, Li P, Li Z, Wu J, Chang J, Shang D, Tian Q, Zhang J, Xie Y, Liu Z, An Y. Deciphering significances of autophagy in the development and metabolism of adipose tissue. Exp Cell Res 2025; 446:114478. [PMID: 39978716 DOI: 10.1016/j.yexcr.2025.114478] [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] [Received: 01/06/2025] [Revised: 02/17/2025] [Accepted: 02/17/2025] [Indexed: 02/22/2025]
Abstract
The mechanisms of adipose tissue activation and inactivation have been a hot topic of research in the last decade, from which countermeasures have been attempted to be found against obesity as well as other lipid metabolism-related diseases, such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. Autophagy has been shown to be closely related to the regulation of adipocyte activity, which is involved in the whole process including white adipocyte differentiation/maturation and brown or beige adipocyte generation/activation. Dysregulation of autophagy in adipose tissue has been demonstrated to be associated with obesity. On this basis, we summarize the pathways and mechanisms of autophagy involved in the regulation of lipid metabolism and present a review of its pathophysiological roles in lipid metabolism-related diseases, in the hope of providing ideas for the treatment of these diseases.
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Affiliation(s)
- Zitao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Haoyuan Peng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengfei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Feiyi Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yutian Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiaoyan Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiayi Chang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Dandan Shang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Qiwen Tian
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Jiawei Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yucheng Xie
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Zhenzhen Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China; Henan Provincial Research Center of Engineering Technology for Nuclear Protein Medical Detection, Zhengzhou Health College, Zhengzhou, 450064, China.
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Booranasuksakul U, Guan Z, Macdonald IA, Tsintzas K, Stephan BCM, Siervo M. Sarcopenic obesity and brain health: A critical appraisal of the current evidence. NUTR BULL 2025; 50:30-43. [PMID: 39799465 DOI: 10.1111/nbu.12725] [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] [Received: 09/04/2024] [Revised: 11/13/2024] [Accepted: 11/13/2024] [Indexed: 01/15/2025]
Abstract
Sarcopenic obesity (SO) is a body composition phenotype derived from the simultaneous presence in the same individual of an increase in fat mass and a decrease in skeletal muscle mass and/or function. Several protocols for the diagnosis of SO have been proposed in the last two decades making prevalence and disease risk estimates of SO heterogeneous and challenging to interpret. Dementia is a complex neurological disorder that significantly impacts patients, carers and healthcare systems. The identification of risk factors for early cognitive impairment and dementia is key to mitigating the forecasted trends of a 2-fold increase in dementia case numbers over the next two decades worldwide. Excess adiposity and sarcopenia have both been independently associated with risk of cognitive impairment and dementia. Whether SO is associated with a greater risk of cognitive impairment and dementia is currently uncertain. This review critically appraises the current evidence on the association between SO with cognitive outcomes and dementia risk. It also discusses some of the putative biological mechanisms that may link the SO phenotype with alteration of brain functions.
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Affiliation(s)
- Uraiporn Booranasuksakul
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Zhongyang Guan
- Curtin School of Population Health, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia
| | - Ian A Macdonald
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Kostas Tsintzas
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Blossom C M Stephan
- Dementia Centre of Excellence, enAble Institute, Curtin University, Bentley, WA, Australia
| | - Mario Siervo
- Curtin School of Population Health, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia
- Dementia Centre of Excellence, enAble Institute, Curtin University, Bentley, WA, Australia
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Zhao Y, Xie W, Duan J, Li F. Probiotic Limosilactobacillus reuteri DSM 17938 Alleviates Acute Liver Injury by Activating the AMPK Signaling via Gut Microbiota-Derived Propionate. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10464-y. [PMID: 39875777 DOI: 10.1007/s12602-025-10464-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2025] [Indexed: 01/30/2025]
Abstract
Limosilactobacillus reuteri DSM 17938 (L. reuteri DSM 17938) was one of the most widely used probiotics in humans for gastrointestinal disorders, but few studies have investigated its role in drug-induced liver injury (DILI). Here, we evaluated the efficacy of L. reuteri DSM 17938 using a mouse model of DILI induced by triptolide. Pregavage of L. reuteri DSM 17938 for 1 week remarkably lowered hepatic inflammatory cytokines level and oxidative stress, with diminished serum alanine transaminase and aspartate aminotransferase levels. Metabolomics and RT-qPCR analysis confirmed its ability in ameliorating TP-disrupted hepatic fatty acid β oxidation. Genome annotation of L. reuteri showed its ability to modulate energy metabolism. Targeted metabolomics demonstrated that L. reuteri DSM 17938 modified the short fatty acid profiles in cecum, especially enhancing propionate levels. Further experiments found that L. reuteri DSM 17938 can activate AMPK signaling by upregulating gut microbiota-derived propionate level, thus restoring impaired mitochondrial biogenesis and energy supply processes to recover energy homeostasis, which leads to diminished ROS production and oxidative stress injury in hepatocytes. Besides, AMPK inhibitor dorsomorphin abolished all the effects on propionate protecting mitochondria and energy metabolism. This study established probiotic therapy of L. reuteri DSM 17938 as a preventive intervention for DILI in clinical. We also revealed that L. reuteri DSM 17938 can activate AMPK signaling by propionate, facilitating a deeper understanding of the action mechanism of L. reuteri DSM 17938 against acute liver injury and contributing to the development of its postbiotics and wider applications.
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Affiliation(s)
- Yuting Zhao
- Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Weiqi Xie
- Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jingyi Duan
- Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Fei Li
- Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Papakonstantinou I, Tsioufis K, Katsi V. Spotlight on the Mechanism of Action of Semaglutide. Curr Issues Mol Biol 2024; 46:14514-14541. [PMID: 39728000 DOI: 10.3390/cimb46120872] [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: 11/21/2024] [Revised: 12/20/2024] [Accepted: 12/21/2024] [Indexed: 12/28/2024] Open
Abstract
Initially intended to control blood glucose levels in patients with type 2 diabetes, semaglutide, a potent glucagon-like peptide 1 analogue, has been established as an effective weight loss treatment by controlling appetite. Integrating the latest clinical trials, semaglutide in patients with or without diabetes presents significant therapeutic efficacy in ameliorating cardiometabolic risk factors and physical functioning, independent of body weight reduction. Semaglutide may modulate adipose tissue browning, which enhances human metabolism and exhibits possible benefits in skeletal muscle degeneration, accelerated by obesity and ageing. This may be attributed to anti-inflammatory, mitochondrial biogenesis, antioxidant and autophagy-regulating effects. However, most of the supporting evidence on the mechanistic actions of semaglutide is preclinical, demonstrated in rodents and not actually confirmed in humans, therefore warranting caution in the interpretation. This article aims to explore potential innovative molecular mechanisms of semaglutide action in restoring the balance of several interlinking aspects of metabolism, pointing to distinct functions in inflammation and oxidative stress in insulin-sensitive musculoskeletal and adipose tissues. Moreover, possible applications in protection from infections and anti-aging properties are discussed. Semaglutide enhancement of the core molecular mechanisms involved in the progress of obesity and diabetes, although mostly preclinical, may provide a framework for future research applications in human diseases overall.
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Affiliation(s)
- Ilias Papakonstantinou
- 4th Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece
| | - Konstantinos Tsioufis
- 1st Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 11527 Athens, Greece
| | - Vasiliki Katsi
- 1st Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 11527 Athens, Greece
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Jing Y, Li M, Li Y, Ma T, Qu Y, Hu B, Xie Y, Li Z. Structural characterization and anti-fatigue mechanism based on the gut-muscle axis of a polysaccharide from Zingiber officinale. Int J Biol Macromol 2024; 283:137621. [PMID: 39547625 DOI: 10.1016/j.ijbiomac.2024.137621] [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] [Received: 05/05/2024] [Revised: 10/09/2024] [Accepted: 11/12/2024] [Indexed: 11/17/2024]
Abstract
This study aimed to characterize the structure of polysaccharide ZOPA extracted from Zingiber officinale and its purified form (ZOPA-1), and to investigate their anti-fatigue mechanisms based on the gut-muscle axis. The study found that the backbone of ZOPA-1 is primarily composed of →3,4)-α-Glcp-1→ and →4,6)-α-Glcp-(1→ linkages, with →4)-α-Glcp(1→ serving as its side chain. In exhaustive swimming experiments with mice, both crude ZOPA and purified ZOPA-1 demonstrated significant anti-fatigue effects, including enhanced glycogen storage, improved antioxidant capacity, reduced accumulation of metabolic waste products, and regulated energy metabolism in the gastrocnemius muscles. These effects may be mediated through the activation of the Keap1-Nrf2/ARE and AMPK/PGC-1α signaling pathways. Furthermore, ZOPA and ZOPA-1 modulated the intestinal flora of mice, increasing diversity, altering abundance, and regulating short-chain fatty acid concentrations, suggesting a potential role of the gut-muscle axis in mediating the anti-fatigue effects. This study provides valuable insights into the complex interplay between polysaccharides, the gut-muscle axis, and exercise-induced fatigue.
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Affiliation(s)
- Yongshuai Jing
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China.
| | - Mingsong Li
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Yingqi Li
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Teng Ma
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Ying Qu
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Beibei Hu
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Yinghua Xie
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China
| | - Zhiwei Li
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang 050018, China.
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11
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Saponaro F, Bertolini A, Baragatti R, Galfo L, Chiellini G, Saba A, D'Urso G. Myokines and Microbiota: New Perspectives in the Endocrine Muscle-Gut Axis. Nutrients 2024; 16:4032. [PMID: 39683426 DOI: 10.3390/nu16234032] [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] [Received: 10/30/2024] [Revised: 11/20/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
This review explores the dual role of skeletal muscle as both a mechanical and endocrine organ, highlighting its contributions to overall health and its adaptability to various inputs such as nutrition, hormones, exercise, and injuries. In addition to its role in metabolism and energy conversion, skeletal muscle secretes signalling molecules called myokines (at rest) and exerkines (during/after physical exercise), which communicate with other organs like the brain, the cardiovascular system, and the immune system. Key molecules such as interleukins, irisin, and myostatin are discussed for their roles in mediating muscle health and inter-organ communication. This work also focuses on the muscle-gut axis, emphasising the bidirectional interaction between skeletal muscle and the gut microbiota, a complex ecosystem influencing immune defence, digestion, and metabolism. Muscle activity, particularly exercise, alters the gut microbial composition, promoting beneficial species, while gut-derived metabolites like short-chain fatty acids (SCFAs) impact muscle metabolism, mitochondrial function, and insulin sensitivity. Dysbiosis, or an imbalanced microbiota, can lead to muscle atrophy, inflammation, and metabolic dysfunction. This evidence highlights emerging research into myokines and exerkines as potential therapeutic targets for managing conditions like muscle decline, ageing, and metabolic diseases through muscle-gut interactions.
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Affiliation(s)
- Federica Saponaro
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Andrea Bertolini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Riccardo Baragatti
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Leonardo Galfo
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Grazia Chiellini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Alessandro Saba
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
| | - Giuseppina D'Urso
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Via Roma 56, 56126 Pisa, Italy
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12
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Wicaksono D, Taslim NA, Lau V, Syahputra RA, Alatas AI, Putra PP, Tallei TE, Tjandrawinata RR, Tsopmo A, Kim B, Nurkolis F. Elucidation of anti-human melanoma and anti-aging mechanisms of compounds from green seaweed Caulerpa racemosa. Sci Rep 2024; 14:27534. [PMID: 39528552 PMCID: PMC11555072 DOI: 10.1038/s41598-024-78464-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
Human melanoma is linked with aging-related disorders, prompting interest in the development of functional foods derived from natural ingredients to mitigate its incidence. Molecules in green seaweeds such as Caulerpa racemosa can serve this purpose due to their anti-tumor and anti-inflammatory properties. A previous work study compounds profiling has been carried out, and in this research the molecular docking studies targeting receptors associated with melanoma (GRP78, IRE1, BRAF) and aging (mTOR, AMPK, SIRT1) identified four promising compound in an extract of C. racemosa. The current study aims to the mechanism of those compounds at a cellular level using the human A375 (BRAF-V600E mutation) and A375 and B16-F10 cell lines. The MTT assay was used to evaluate the potential of GSCRE compounds against A375 and B16-F10 cell lines, with comparisons made to normal HDFa cell lines. Results indicated that compound C2, also known as Caulersin, demonstrated a significantly different ∆G affinity binding score compared to the control drug Dabrafenib. GSCRE crude extract, particularly C2, showed potential in modulating mTOR, AMPK, and SIRT1 pathways and downregulating GRP78, IRE1, and BRAF signaling (p < 0.05). Interestingly, C2 was less effective in suppressing A375 and B16-F10 cell lines (LD50 C2 < LD50 Dabrafenib/control), with its LD50 value nearly matching that of the Trametinib control in B16-F10 cell lines. Consequently, GSCRE, especially C2 or Caulersin, shows promise as a new molecule for developing functional foods to combat aging and human melanoma. However, further in vivo studies and clinical trials are necessary to confirm these findings.
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Affiliation(s)
- Danar Wicaksono
- Alumnus Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Nurpudji Astuti Taslim
- Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, 90245, Indonesia
| | - Vincent Lau
- Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Rony Abdi Syahputra
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia
| | - Aiman Idrus Alatas
- Program of Clinical Microbiology Residency, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Purnawan Pontana Putra
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Andalas, Padang, 25163, Indonesia
| | - Trina Ekawati Tallei
- Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, 95115, Indonesia
| | - Raymond Rubianto Tjandrawinata
- Center for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia
| | - Apollinaire Tsopmo
- Food Science and Nutrition Program, Department of Chemistry, Carleton University, 1125 Colonel by Drive, Ottawa, ON, K1S 5B6, Canada
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Kyungheedae-Ro 26, Dong-Daemun-Gu, Seoul, 05254, South Korea
| | - Fahrul Nurkolis
- Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia.
- Medical Research Center of Indonesia (MERCIE), Surabaya, 60281, Indonesia.
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13
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Zhao J, Duan L, Li J, Yao C, Wang G, Mi J, Yu Y, Ding L, Zhao Y, Yan G, Li J, Zhao Z, Wang X, Li M. New insights into the interplay between autophagy, gut microbiota and insulin resistance in metabolic syndrome. Biomed Pharmacother 2024; 176:116807. [PMID: 38795644 DOI: 10.1016/j.biopha.2024.116807] [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] [Received: 03/12/2024] [Revised: 05/20/2024] [Accepted: 05/20/2024] [Indexed: 05/28/2024] Open
Abstract
Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.
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Affiliation(s)
- Jinyue Zhao
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Liyun Duan
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Jiarui Li
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Chensi Yao
- Molecular Biology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Guoqiang Wang
- The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Jia Mi
- The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Yongjiang Yu
- The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Lu Ding
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Yunyun Zhao
- The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Guanchi Yan
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Jing Li
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Zhixuan Zhao
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Xiuge Wang
- The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
| | - Min Li
- Molecular Biology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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14
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Liu S, He Y, Zhang Y, Zhang Z, Huang K, Deng L, Liao B, Zhong Y, Feng J. Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms. Gut Microbes 2023; 15:2290331. [PMID: 38073096 PMCID: PMC10730151 DOI: 10.1080/19490976.2023.2290331] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
The global population is aging and age-related cardiovascular disease is increasing. Even after controlling for cardiovascular risk factors, readmission and mortality rates remain high. In recent years, more and more in-depth studies have found that the composition of the gut microbiota and its metabolites, such as trimethylamine N-oxide (TMAO), bile acids (BAs), and short-chain fatty acids (SCFAs), affect the occurrence and development of age-related cardiovascular diseases through a variety of molecular pathways, providing a new target for therapy. In this review, we discuss the relationship between the gut microbiota and age-related cardiovascular diseases, and propose that the gut microbiota could be a new therapeutic target for preventing and treating cardiovascular diseases.
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Affiliation(s)
- Siqi Liu
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Yufeng He
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Yali Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Zhaolun Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Keming Huang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Li Deng
- Department of Rheumatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Bin Liao
- Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Yi Zhong
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Jian Feng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
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15
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Sadeghi A, Niknam M, Momeni-Moghaddam MA, Shabani M, Aria H, Bastin A, Teimouri M, Meshkani R, Akbari H. Crosstalk between autophagy and insulin resistance: evidence from different tissues. Eur J Med Res 2023; 28:456. [PMID: 37876013 PMCID: PMC10599071 DOI: 10.1186/s40001-023-01424-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023] Open
Abstract
Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.
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Affiliation(s)
- Asie Sadeghi
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Niknam
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Maryam Shabani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Aria
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Alireza Bastin
- Clinical Research Development Center "The Persian Gulf Martyrs" Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Maryam Teimouri
- Department of Biochemistry, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Akbari
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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16
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Gross DC, Cheever CR, Batsis JA. Understanding the development of sarcopenic obesity. Expert Rev Endocrinol Metab 2023; 18:469-488. [PMID: 37840295 PMCID: PMC10842411 DOI: 10.1080/17446651.2023.2267672] [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: 03/02/2023] [Accepted: 10/03/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION Sarcopenic obesity (SarcO) is defined as the confluence of reduced muscle mass and function and excess body fat. The scientific community is increasingly recognizing this syndrome, which affects a subgroup of persons across their lifespans and places them at synergistically higher risk of significant medical comorbidity and disability than either sarcopenia or obesity alone. Joint efforts in clinical and research settings are imperative to better understand this syndrome and drive the development of urgently needed future interventions. AREAS COVERED Herein, we describe the ongoing challenges in defining sarcopenic obesity and the current state of the science regarding its epidemiology and relationship with adverse events. The field has demonstrated an emergence of data over the past decade which we will summarize in this article. While the etiology of sarcopenic obesity is complex, we present data on the underlying pathophysiological mechanisms that are hypothesized to promote its development, including age-related changes in body composition, hormonal changes, chronic inflammation, and genetic predisposition. EXPERT OPINION We describe emerging areas of future research that will likely be needed to advance this nascent field, including changes in clinical infrastructure, an enhanced understanding of the lifecourse, and potential treatments.
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Affiliation(s)
- Danae C. Gross
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - C. Ray Cheever
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - John A. Batsis
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Geriatric Medicine, UNC School of Medicine, Chapel Hill, North Carolina, USA
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17
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Wang Z, Liu J, Li F, Ma S, Zhao L, Ge P, Wen H, Zhang Y, Liu X, Luo Y, Yao J, Zhang G, Chen H. Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway. Microbiol Spectr 2023; 11:e0366422. [PMID: 37338348 PMCID: PMC10434154 DOI: 10.1128/spectrum.03664-22] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 05/24/2023] [Indexed: 06/21/2023] Open
Abstract
The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.
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Affiliation(s)
- Zhengjian Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Jin Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Fan Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Shurong Ma
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Liang Zhao
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Peng Ge
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Haiyun Wen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Yibo Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Xiaojun Liu
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Department of Anesthesiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Jiaqi Yao
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Department of Anesthesiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
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Zhou Y, Chu Z, Luo Y, Yang F, Cao F, Luo F, Lin Q. Dietary Polysaccharides Exert Anti-Fatigue Functions via the Gut-Muscle Axis: Advances and Prospectives. Foods 2023; 12:3083. [PMID: 37628082 PMCID: PMC10453516 DOI: 10.3390/foods12163083] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/11/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.
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Affiliation(s)
- Yaping Zhou
- National Engineering Research Center of Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, No. 498, Shaoshan Road, Changsha 410004, China; (Y.Z.); (Z.C.); (F.Y.); (F.L.)
| | - Zhongxing Chu
- National Engineering Research Center of Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, No. 498, Shaoshan Road, Changsha 410004, China; (Y.Z.); (Z.C.); (F.Y.); (F.L.)
| | - Yi Luo
- Department of Clinical Medicine, Medical College of Xiangya, Central South University, Changsha 410008, China;
| | - Feiyan Yang
- National Engineering Research Center of Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, No. 498, Shaoshan Road, Changsha 410004, China; (Y.Z.); (Z.C.); (F.Y.); (F.L.)
| | - Fuliang Cao
- Co-Innovation Center for the Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing 210037, China;
| | - Feijun Luo
- National Engineering Research Center of Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, No. 498, Shaoshan Road, Changsha 410004, China; (Y.Z.); (Z.C.); (F.Y.); (F.L.)
| | - Qinlu Lin
- National Engineering Research Center of Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, No. 498, Shaoshan Road, Changsha 410004, China; (Y.Z.); (Z.C.); (F.Y.); (F.L.)
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19
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Fan C, Wang G, Chen M, Li Y, Tang X, Dai Y. Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice. Chin J Nat Med 2023; 21:411-422. [PMID: 37407172 DOI: 10.1016/s1875-5364(23)60403-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Indexed: 07/07/2023]
Abstract
Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.
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Affiliation(s)
- Cailian Fan
- College of Medicine, Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine, Pingdingshan University, Pingdingshan 467000, China.
| | - Guan Wang
- Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu 610041, China.
| | - Miao Chen
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
| | - Yao Li
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
| | - Xiyang Tang
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
| | - Yi Dai
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
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20
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Huang A, Ji L, Li Y, Li Y, Yu Q. Gut microbiome plays a vital role in post-stroke injury repair by mediating neuroinflammation. Int Immunopharmacol 2023; 118:110126. [PMID: 37031605 DOI: 10.1016/j.intimp.2023.110126] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/18/2023] [Accepted: 03/29/2023] [Indexed: 04/11/2023]
Abstract
Cerebral stroke is a common neurological disease and often causes severe neurological deficits. With high morbidity, mortality, and disability rates, stroke threatens patients' life quality and brings a heavy economic burden on society. Ischemic cerebral lesions incur pathological changes as well as spontaneous nerve repair following stroke. Strategies such as drug therapy, physical therapy, and surgical treatment, can ameliorate blood and oxygen supply in the brain, hamper the inflammatory responses and maintain the structural and functional integrity of the brain. The gut microbiome, referred to as the "second genome" of the human body, participates in the regulation of multiple physiological functions including metabolism, digestion, inflammation, and immunity. The gut microbiome is not only inextricably associated with dangerous factors pertaining to stroke, including high blood pressure, diabetes, obesity, and atherosclerosis, but also influences stroke occurrence and prognosis. AMPK functions as a hub of metabolic control and is responsible for the regulation of metabolic events under physiological and pathological conditions. The AMPK mediators have been found to exert dual roles in regulating gut microbiota and neuroinflammation/neuronal apoptosis in stroke. In this study, we reviewed the role of the gut microbiome in cerebral stroke and the underlying mechanism of the AMPK signaling pathway in stroke. AMPK mediators in nerve repair and the regulation of intestinal microbial balance were also summarized.
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Affiliation(s)
- Airu Huang
- Department of Rehabilitation Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Ling Ji
- Department of Rehabilitation Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Yamei Li
- Department of Rehabilitation Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Yufeng Li
- Department of Rehabilitation Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
| | - Qian Yu
- Department of Rehabilitation Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
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21
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Wang H, Su J, Yu M, Xia Y, Wei Y. PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action. Front Pharmacol 2023; 14:1169019. [PMID: 37089944 PMCID: PMC10117990 DOI: 10.3389/fphar.2023.1169019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 03/30/2023] [Indexed: 04/08/2023] Open
Abstract
Osteoarthritis (OA) is one of the most common degenerative joint diseases, often involving the entire joint. The degeneration of articular cartilage is an important feature of OA, and there is growing evidence that the mitochondrial biogenesis master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) exert a chondroprotective effect. PGC-1α delays the development and progression of OA by affecting mitochondrial biogenesis, oxidative stress, mitophagy and mitochondrial DNA (mtDNA) replication in chondrocytes. In addition, PGC-1α can regulate the metabolic abnormalities of OA chondrocytes and inhibit chondrocyte apoptosis. In this paper, we review the regulatory mechanisms of PGC-1α and its effects on OA chondrocytes, and introduce potential drugs and novel nanohybrid for the treatment of OA which act by affecting the activity of PGC-1α. This information will help to further elucidate the pathogenesis of OA and provide new ideas for the development of therapeutic strategies for OA.
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Affiliation(s)
- Haochen Wang
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jianbang Su
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Minghao Yu
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Yang Xia, ; Yingliang Wei,
| | - Yingliang Wei
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Yang Xia, ; Yingliang Wei,
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Singh S, Sharma P, Sarma DK, Kumawat M, Tiwari R, Verma V, Nagpal R, Kumar M. Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer. Cancers (Basel) 2023; 15:1913. [PMID: 36980799 PMCID: PMC10047102 DOI: 10.3390/cancers15061913] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/12/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
The complexity and variety of gut microbiomes within and among individuals have been extensively studied in recent years in connection to human health and diseases. Our growing understanding of the bidirectional communication between metabolic diseases and the gut microbiome has also highlighted the significance of gut microbiome dysbiosis in the genesis and development of obesity-related cancers. Therefore, it is crucial to comprehend the possible role of the gut microbiota in the crosstalk between obesity and colorectal cancer (CRC). Through the induction of gut microbial dysbiosis, gut epithelial barrier impairment, metabolomic dysregulation, chronic inflammation, or dysregulation in energy harvesting, obesity may promote the development of colorectal tumors. It is well known that strategies for cancer prevention and treatment are most effective when combined with a healthy diet, physical activity, and active lifestyle choices. Recent studies also suggest that an improved understanding of the complex linkages between the gut microbiome and various cancers as well as metabolic diseases can potentially improve cancer treatments and overall outcomes. In this context, we herein review and summarize the clinical and experimental evidence supporting the functional role of the gut microbiome in the pathogenesis and progression of CRC concerning obesity and its metabolic correlates, which may pave the way for the development of novel prognostic tools for CRC prevention. Therapeutic approaches for restoring the microbiome homeostasis in conjunction with cancer treatments are also discussed herein.
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Affiliation(s)
- Samradhi Singh
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
| | - Poonam Sharma
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
| | - Devojit Kumar Sarma
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
| | - Manoj Kumawat
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
| | - Rajnarayan Tiwari
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
| | - Vinod Verma
- Stem Cell Research Centre, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow 226014, India
| | - Ravinder Nagpal
- Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL 32302, USA
| | - Manoj Kumar
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal 462030, India
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23
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A Minireview Exploring the Interplay of the Muscle-Gut-Brain (MGB) Axis to Improve Knowledge on Mental Disorders: Implications for Clinical Neuroscience Research and Therapeutics. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8806009. [PMID: 36160716 PMCID: PMC9499796 DOI: 10.1155/2022/8806009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 08/17/2022] [Indexed: 11/24/2022]
Abstract
What benefit might emerge from connecting clinical neuroscience with microbiology and exercise science? What about the influence of the muscle-gut-brain (MGB) axis on mental health? The gut microbiota colonizes the intestinal tract and plays a pivotal role in digestion, production of vitamins and immune system development, but it is also able to exert a particular effect on psychological well-being and appears to play a critical role in regulating several muscle metabolic pathways. Endogenous and exogenous factors may cause dysbiosis, with relevant consequences on the composition and function of the gut microbiota that may also modulate muscle responses to exercise. The capacity of specific psychobiotics in ameliorating mental health as complementary strategies has been recently suggested as a novel treatment for some neuropsychiatric diseases. Moreover, physical exercise can modify qualitative and quantitative composition of the gut microbiota and alleviate certain psychopathological symptoms. In this minireview, we documented evidence about the impact of the MGB axis on mental health, which currently appears to be a possible target in the context of a multidimensional intervention mainly including pharmacological and psychotherapeutic treatments, especially for depressive mood.
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24
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Hui Y, Cui B, Wang X, Sun M, Li Y, Yang W, Guo G, Mao L, Yu Z, Fan X, Sun C. Sarcopenic obesity in liver disease: Handling both sides of the penny. PORTAL HYPERTENSION & CIRRHOSIS 2022; 1:42-56. [DOI: 10.1002/poh2.10] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/14/2022] [Indexed: 01/03/2025]
Abstract
AbstractSkeletal muscle and fat tissue show distinct pathophysiological roles and pivotal functions. The culmination of muscle wasting and fat accumulation represents an opposite terminal of each state. Specifically, this situation has been designated as sarcopenic obesity. However, sarcopenic obesity still lacks a unanimous definition, diagnostic criteria, and generalized modalities for assessment in the context of versatile liver diseases. Moreover, the underpinning mechanisms by which a combination of abnormal skeletal muscle and fat tissue leads to the progression of liver disease and impairs health‐related consequences are still elusive. Additionally, the interplay between skeletal muscle and fat, and the driving factors that shift different body compositions are not well understood. Therefore, in this review, we discuss skeletal muscle and fat components, with the purpose of conceptualization, as well as interpret their roles in liver diseases. We focus on the definitions, diagnostic criteria, and currently available measurements for sarcopenic obesity in the literature. We comprehensively discuss recent data and evidence regarding the potential role of sarcopenic obesity in the development and progression of numerous liver diseases and associated conditions, including nonalcoholic fatty liver disease, chronic viral hepatitis, cirrhosis, and liver transplantation. Furthermore, explicit information related to the pathogenesis of sarcopenic obesity from basic research is also provided in this narrative review. Finally, we discuss, from the clinical perspective of view, how to manage sarcopenic obesity using nutritional, physical, and pharmacological methods.
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Affiliation(s)
- Yangyang Hui
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Binxin Cui
- Department of Gastroenterology Tianjin Medical University General Hospital Airport Hospital Tianjin China
| | - Xiaoyu Wang
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Mingyu Sun
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Yifan Li
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Lihong Mao
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Xiaofei Fan
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
| | - Chao Sun
- Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin China
- Department of Gastroenterology Tianjin Medical University General Hospital Airport Hospital Tianjin China
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25
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Li G, Jin B, Fan Z. Mechanisms Involved in Gut Microbiota Regulation of Skeletal Muscle. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2151191. [PMID: 35633886 PMCID: PMC9132697 DOI: 10.1155/2022/2151191] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/03/2022] [Indexed: 12/12/2022]
Abstract
Skeletal muscle is one of the largest organs in the body and is essential for maintaining quality of life. Loss of skeletal muscle mass and function can lead to a range of adverse consequences. The gut microbiota can interact with skeletal muscle by regulating a variety of processes that affect host physiology, including inflammatory immunity, protein anabolism, energy, lipids, neuromuscular connectivity, oxidative stress, mitochondrial function, and endocrine and insulin resistance. It is proposed that the gut microbiota plays a role in the direction of skeletal muscle mass and work. Even though the notion of the gut microbiota-muscle axis (gut-muscle axis) has been postulated, its causal link is still unknown. The impact of the gut microbiota on skeletal muscle function and quality is described in detail in this review.
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Affiliation(s)
- Guangyao Li
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
- Department of Central Laboratory, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
| | - Binghui Jin
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
- Department of Central Laboratory, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
| | - Zhe Fan
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
- Department of Central Laboratory, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, China
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26
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Targeting AMPK signaling in ischemic/reperfusion injury: From molecular mechanism to pharmacological interventions. Cell Signal 2022; 94:110323. [DOI: 10.1016/j.cellsig.2022.110323] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 12/16/2022]
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27
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Huang R. Gut Microbiota: A Key Regulator in the Effects of Environmental Hazards on Modulates Insulin Resistance. Front Cell Infect Microbiol 2022; 11:800432. [PMID: 35111696 PMCID: PMC8801599 DOI: 10.3389/fcimb.2021.800432] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 11/30/2021] [Indexed: 12/17/2022] Open
Abstract
Insulin resistance is a hallmark of Alzheimer’s disease (AD), type II diabetes (T2D), and Parkinson’s disease (PD). Emerging evidence indicates that these disorders are typically characterized by alterations in the gut microbiota composition, diversity, and their metabolites. Currently, it is understood that environmental hazards including ionizing radiation, toxic heavy metals, pesticides, particle matter, and polycyclic aromatic hydrocarbons are capable of interacting with gut microbiota and have a non-beneficial health effect. Based on the current study, we propose the hypothesis of “gut microenvironment baseline drift”. According to this “baseline drift” theory, gut microbiota is a temporarily combined cluster of species sharing the same environmental stresses for a short period, which would change quickly under the influence of different environmental factors. This indicates that the microbial species in the gut do not have a long-term relationship; any split, division, or recombination may occur in different environments. Nonetheless, the “baseline drift” theory considers the critical role of the response of the whole gut microbiome. Undoubtedly, this hypothesis implies that the gut microbiota response is not merely a “cross junction” switch; in contrast, the human health or disease is a result of a rich palette of gut-microbiota-driven multiple-pathway responses. In summary, environmental factors, including hazardous and normal factors, are critical to the biological impact of the gut microbiota responses and the dual effect of the gut microbiota on the regulation of biological functions. Novel appreciation of the role of gut microbiota and environmental hazards in the insulin resistance would shed new light on insulin resistance and also promote the development of new research direction and new overcoming strategies for patients.
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28
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Lee SJ, Chandrasekran P, Mazucanti CH, O’Connell JF, Egan JM, Kim Y. Dietary curcumin restores insulin homeostasis in diet-induced obese aged mice. Aging (Albany NY) 2022; 14:225-239. [PMID: 35017319 PMCID: PMC8791219 DOI: 10.18632/aging.203821] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/29/2021] [Indexed: 06/14/2023]
Abstract
Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.
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Affiliation(s)
- Su-Jeong Lee
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA
| | - Prabha Chandrasekran
- Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA
| | - Caio Henrique Mazucanti
- Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA
| | - Jennifer F. O’Connell
- Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA
| | - Josephine M. Egan
- Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA
| | - Yoo Kim
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA
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Coto-Montes A, González-Blanco L, Antuña E, Menéndez-Valle I, Bermejo-Millo JC, Caballero B, Vega-Naredo I, Potes Y. The Interactome in the Evolution From Frailty to Sarcopenic Dependence. Front Cell Dev Biol 2021; 9:792825. [PMID: 34926470 PMCID: PMC8675940 DOI: 10.3389/fcell.2021.792825] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 11/11/2021] [Indexed: 12/01/2022] Open
Abstract
Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones. Overweight is a recognized cause of frailty in aging, so we studied the altered mechanisms in overweight independent elderly and evaluated their aggravation in dependent elderly. This evidence of the evolution of previously altered mechanisms would significantly support their role as real biomarkers of frailty. The results showed a preponderant role of autophagy in interactome control at both different functional points, modulating other essential mechanisms in the cell, such as mitochondrial capacity or oxidative stress. Thus, the overweight provoked in the muscle of the elderly an overload of autophagy that kept cell survival in apparently healthy individuals. This excessive and permanent autophagic effort did not seem to be able to be maintained over time. Indeed, in dependent elderly, the muscle showed a total autophagic inactivity, with devastating effects on the survival of the cell, which showed clear signs of apoptosis, and reduced functional capacity. The frail elderly are in a situation of weakness that is a precursor of dependence that can still be prevented if detection is early. Hence biomarkers are essential in this context.
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Affiliation(s)
- Ana Coto-Montes
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Laura González-Blanco
- Área de Sistemas de Producción Animal, Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), Villaviciosa, Spain
| | - Eduardo Antuña
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Iván Menéndez-Valle
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Juan Carlos Bermejo-Millo
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Beatriz Caballero
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Ignacio Vega-Naredo
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
| | - Yaiza Potes
- Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain
- Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Oviedo, Spain
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Zhao J, Huang Y, Yu X. A Narrative Review of Gut-Muscle Axis and Sarcopenia: The Potential Role of Gut Microbiota. Int J Gen Med 2021; 14:1263-1273. [PMID: 33880058 PMCID: PMC8053521 DOI: 10.2147/ijgm.s301141] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022] Open
Abstract
Sarcopenia is a multifactorial disease related to aging, chronic inflammation, insufficient nutrition, and physical inactivity. Previous studies have suggested that there is a relationship between sarcopenia and gut microbiota,namely, the gut-muscle axis. The present review highlights that the gut microbiota can affect muscle mass and muscle function from inflammation and immunity,substance and energy metabolism, endocrine and insulin sensitivity, etc., directly or indirectly establishing a connection with sarcopenia, thereby realizing the “gut-muscle axis”.
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Affiliation(s)
- Jiaxi Zhao
- Huadong Hospital Affiliated to Fudan University, Shanghai, People's Republic of China
| | - Yiqin Huang
- Huadong Hospital Affiliated to Fudan University, Shanghai, People's Republic of China
| | - Xiaofeng Yu
- Huadong Hospital Affiliated to Fudan University, Shanghai, People's Republic of China
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