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1
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Pham TN, Schelling RE, Loh KH. Parkinson's disease and metabolic disorders, understanding their shared co-morbidity through the autonomic nervous system. ADVANCES IN GENETICS 2025; 113:199-247. [PMID: 40409798 DOI: 10.1016/bs.adgen.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2025]
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor dysfunctions. Its pathological hallmark is the aggregation of ɑ-synuclein in the central nervous system (CNS), leading to widespread loss of dopaminergic neurons in the substantia nigra (SN). Interestingly, metabolic disorders localized in the periphery, such as diabetes mellitus, frequently co-occur with PD. Emerging evidence highlights a bidirectional relationship: metabolic diseases may accelerate PD progression, while PD can exacerbate metabolic dysfunction. Beyond these associations, a growing body of research suggests that dysfunction in the peripheral nervous system, the primary communication bridge between the brain and peripheral organs, plays a critical role in these comorbidities. Autonomic nerve perturbation may accelerate dopaminergic neuronal loss in the SN and exacerbate metabolic dysregulation. This chapter synthesizes current evidence linking autonomic dysfunction with the progression of PD and related metabolic disorders, and it explores innovative therapeutic strategies leveraging this bidirectional relationship to address PD progression.
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Affiliation(s)
- Thanh N Pham
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States
| | - Rebecca E Schelling
- Department of Pharmacology, Yale University School of Medicine, New Haven, CT, United States
| | - Ken H Loh
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States; Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT, United States.
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2
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Zheng X, Zhu J, Haedi AR, Zhou M. The effect of curcumin supplementation on glycemic indices in adults: A meta-analysis of meta-analyses. Prostaglandins Other Lipid Mediat 2024; 175:106908. [PMID: 39270815 DOI: 10.1016/j.prostaglandins.2024.106908] [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: 06/11/2024] [Revised: 09/04/2024] [Accepted: 09/10/2024] [Indexed: 09/15/2024]
Abstract
Curcumin, an inherent polyphenolic compound, has the potential to influence glycemic indices. Nevertheless, the conclusions drawn from extant meta-analyses remain contentious. To determine the impact of curcumin supplementation on these indices, the current umbrella meta-analysis included existing systematic reviews and meta-analyses. A thorough systematic search was conducted using databases Embase, PubMed, WOS, Scopus, and the Cochrane Library to acquire peer-reviewed literature published before January 2024. The random-effects model was employed to conduct a meta-analysis. The present analysis incorporated a total of 22 meta-analytic studies. The findings of our study indicate that the administration of curcumin supplements leads to a significant decrease in fasting blood sugar levels (FBS) (ES: -1.63; 95 % CI: -2.36, -0.89, P<0.001; I2=88.4 %, P<0.001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (ES: -0.38; 95 % CI: -0.48, -0.28, P<0.001; I2=35.9 %, P=0.142), hemoglobin A1c (HbA1c) (ES: -0.44; 95 % CI: -0.67, -0.21, P<0.001; I2=65.0 %, P=0.014), and insulin (ES: -0.86; 95 % CI: -1.52, -0.21, P=0.010; I2=92.5 %, P<0.001). The results of this study suggest that the administration of curcumin supplements may be a beneficial intervention for enhancing glycemic indices.
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Affiliation(s)
- Xiaoying Zheng
- Nursing Department, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Jinhua Zhu
- Second Department of Surgery, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Amir Reza Haedi
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Miaomiao Zhou
- Third Department of Surgery, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, China.
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3
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Al Harake SN, Abedin Y, Hatoum F, Nassar NZ, Ali A, Nassar A, Kanaan A, Bazzi S, Azar S, Harb F, Ghadieh HE. Involvement of a battery of investigated genes in lipid droplet pathophysiology and associated comorbidities. Adipocyte 2024; 13:2403380. [PMID: 39329369 PMCID: PMC11445895 DOI: 10.1080/21623945.2024.2403380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 08/29/2024] [Accepted: 09/05/2024] [Indexed: 09/28/2024] Open
Abstract
Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating lipid flux within white adipose tissue (WAT). The physiological function of adipocytes and LDs can be compromised by mutations in several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly in the form of dyslipidemia, ectopic fat accumulation, and insulin resistance. In this review, we delineate the effects of mutations and deficiencies in genes - CIDEC, PPARG, BSCL2, AGPAT2, PLIN1, LIPE, LMNA, CAV1, CEACAM1, and INSR - involved in lipid droplet metabolism and their associated pathophysiological impairments, highlighting their roles in the development of lipodystrophies and metabolic dysfunction.
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Affiliation(s)
- Sami N. Al Harake
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Yasamin Abedin
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Fatema Hatoum
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Nour Zahraa Nassar
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Ali Ali
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Aline Nassar
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Amjad Kanaan
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Samer Bazzi
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Sami Azar
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Frederic Harb
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
| | - Hilda E. Ghadieh
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon
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4
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Sabatini S, Sen P, Carli F, Pezzica S, Rosso C, Lembo E, Verrastro O, Daly A, Govaere O, Cockell S, Hyötyläinen T, Mingrone G, Bugianesi E, Anstee QM, Orešič M, Gastaldelli A. Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis. Cell Rep Med 2024; 5:101820. [PMID: 39566466 PMCID: PMC11604487 DOI: 10.1016/j.xcrm.2024.101820] [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: 08/25/2023] [Revised: 07/25/2024] [Accepted: 10/16/2024] [Indexed: 11/22/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-2H2-glucose, U-2H5-glycerol) and liver-specific genome-scale metabolic models (GEMs). Tracer-measured HGP is increased with liver fibrosis and inflammation, but not steatosis, and is associated with lipolysis and IR. The GEM-derived gluconeogenesis is elevated due to high glucogenic/energy metabolite uptakes (lactate, glycerol, and free fatty acid [FFA]), and the expression of insulin action genes (IRS1, IRS2, and AKT2) is reduced in MASH with fibrosis F2-F4, with/without T2D, suggesting these as putative mechanisms for increased fasting HGP and hyperglycemia. In conclusion, elevated HGP, lipolysis, and IR help to explain the mechanisms for the increased risk of hyperglycemia and T2D in MASH.
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Affiliation(s)
- Silvia Sabatini
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, 56121 Pisa, Italy
| | - Partho Sen
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
| | - Fabrizia Carli
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, 56121 Pisa, Italy
| | - Samantha Pezzica
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, 56121 Pisa, Italy
| | - Chiara Rosso
- Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, 10124 Turin, Italy
| | - Erminia Lembo
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Ornella Verrastro
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ann Daly
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Olivier Govaere
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Department of Imaging and Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium
| | - Simon Cockell
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Tuulia Hyötyläinen
- School of Science and Technology, Örebro University, 70281 Örebro, Sweden
| | - Geltrude Mingrone
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College Hospital, London, UK
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, 10124 Turin, Italy
| | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne NE7 7DN, UK
| | - Matej Orešič
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; School of Medical Sciences, Örebro University, 70281 Örebro, Sweden.
| | - Amalia Gastaldelli
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, 56121 Pisa, Italy; Diabetes Division, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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5
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Wang X, Rusinova R, Gregorio GG, Boudker O. Free fatty acids inhibit an ion-coupled membrane transporter by dissipating the ion gradient. J Biol Chem 2024; 300:107955. [PMID: 39491650 DOI: 10.1016/j.jbc.2024.107955] [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] [Received: 06/24/2024] [Revised: 10/16/2024] [Accepted: 10/21/2024] [Indexed: 11/05/2024] Open
Abstract
Glutamate is the main excitatory transmitter in the mammalian central nervous system; glutamate transporters keep the synaptic glutamate concentrations at bay for normal brain function. Arachidonic acid (AA), docosahexaenoic acid, and other unsaturated fatty acids modulate glutamate transporters in cell- and tissue slices-based studies. Here, we investigated their effect and mechanism using a purified archaeal glutamate transporter homolog reconstituted into the lipid membranes. AA, docosahexaenoic acid, and related fatty acids irreversibly inhibited the sodium-dependent concentrative substrate uptake into lipid vesicles within the physiologically relevant concentration range. In contrast, AA did not inhibit amino acid exchange across the membrane. The length and unsaturation of the aliphatic tail affect inhibition, and the free carboxylic headgroup is necessary. The inhibition potency did not correlate with the fatty acid effects on the bilayer deformation energies. AA does not affect the conformational dynamics of the protein, suggesting it does not inhibit structural transitions necessary for transport. Single-transporter and membrane voltage assays showed that AA and related fatty acids mediate cation leak, dissipating the driving sodium gradient. Thus, such fatty acids can act as cation ionophores, suggesting a general modulatory mechanism of membrane channels and ion-coupled transporters.
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Affiliation(s)
- Xiaoyu Wang
- Department of Physiology & Biophysics, Weill Cornell Medicine, New York, New York, USA.
| | - Radda Rusinova
- Department of Physiology & Biophysics, Weill Cornell Medicine, New York, New York, USA
| | - G Glenn Gregorio
- Department of Physiology & Biophysics, Weill Cornell Medicine, New York, New York, USA; Howard Hughes Medical Institute, Weill Cornell Medicine, New York, New York, USA
| | - Olga Boudker
- Department of Physiology & Biophysics, Weill Cornell Medicine, New York, New York, USA; Howard Hughes Medical Institute, Weill Cornell Medicine, New York, New York, USA.
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6
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Zhang YY, Li YJ, Xue CD, Li S, Gao ZN, Qin KR. Effects of T2DM on cancer progression: pivotal precipitating factors and underlying mechanisms. Front Endocrinol (Lausanne) 2024; 15:1396022. [PMID: 39290325 PMCID: PMC11405243 DOI: 10.3389/fendo.2024.1396022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 08/21/2024] [Indexed: 09/19/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation.
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Affiliation(s)
- Yu-Yuan Zhang
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
- School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, China
| | - Yong-Jiang Li
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
- School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, China
| | - Chun-Dong Xue
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
- School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, China
| | - Shen Li
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
| | - Zheng-Nan Gao
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
| | - Kai-Rong Qin
- Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China
- School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, China
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7
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Yang D. TRPA1-Related Diseases and Applications of Nanotherapy. Int J Mol Sci 2024; 25:9234. [PMID: 39273183 PMCID: PMC11395144 DOI: 10.3390/ijms25179234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 07/30/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects.
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Affiliation(s)
- Dongki Yang
- Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
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8
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Sourianarayanane A, Brydges CR, McCullough AJ. Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity. Clin Res Hepatol Gastroenterol 2024; 48:102402. [PMID: 38909684 DOI: 10.1016/j.clinre.2024.102402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/12/2024] [Accepted: 06/18/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Diabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation. METHODS A comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both. RESULTS MASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p < 0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings. CONCLUSION The changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.
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Affiliation(s)
- Achuthan Sourianarayanane
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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9
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Mazgelytė E, Karčiauskaitė D. Cortisol in metabolic syndrome. Adv Clin Chem 2024; 123:129-156. [PMID: 39181620 DOI: 10.1016/bs.acc.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Abstract
Cortisol, a stress hormone, plays a crucial role in regulating metabolic, hemodynamic, inflammatory, and behavioral processes. Its secretion is governed by the hypothalamic-pituitary-adrenal axis. However, prolonged activation of this axis and increased cortisol bioavailability in tissues can result in detrimental metabolic effects. Chronic exposure to excessive cortisol is associated with insulin resistance and visceral obesity, both significant contributors to metabolic syndrome. This review delves into the regulation of the hypothalamic-pituitary-adrenal axis, the molecular mechanisms underlying cortisol synthesis and its actions, as well as the key factors influencing cortisol bioavailability. Furthermore, it provides a summary of available clinical research data on the involvement of cortisol in metabolic syndrome, alongside a discussion on the various biomatrices used for cortisol measurement in clinical settings.
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Affiliation(s)
- Eglė Mazgelytė
- Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
| | - Dovilė Karčiauskaitė
- Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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10
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Cai M, Wan J, Cai K, Li S, Du X, Song H, Sun W, Hu J. The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity. Int J Obes (Lond) 2024; 48:749-763. [PMID: 38379083 DOI: 10.1038/s41366-024-01490-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/22/2024]
Abstract
Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer's disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.
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Affiliation(s)
- Ming Cai
- Jinshan District Central Hospital affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, 201599, China
| | - Jian Wan
- Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai, 201299, China
| | - Keren Cai
- College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Shuyao Li
- College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xinlin Du
- College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Haihan Song
- Central Lab, Shanghai Key Laboratory of Pathogenic Fungi Medical Testing, Shanghai Pudong New Area People's Hospital, Shanghai, 201299, China
| | - Wanju Sun
- Central Lab, Shanghai Key Laboratory of Pathogenic Fungi Medical Testing, Shanghai Pudong New Area People's Hospital, Shanghai, 201299, China.
| | - Jingyun Hu
- Central Lab, Shanghai Key Laboratory of Pathogenic Fungi Medical Testing, Shanghai Pudong New Area People's Hospital, Shanghai, 201299, China.
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11
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Son WH, Ha MS, Park TJ. Effect of physical activity on free fatty acids, insulin resistance, and blood pressure in obese older women. Phys Act Nutr 2024; 28:1-6. [PMID: 39097991 PMCID: PMC11298281 DOI: 10.20463/pan.2024.0009] [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: 03/06/2024] [Revised: 03/23/2024] [Accepted: 04/03/2024] [Indexed: 08/06/2024] Open
Abstract
PURPOSE Obesity is characterized by a progressive increase in body fat accompanied by insulin resistance (IR) and elevated blood pressure (BP), and presents significant health risks, particularly in aged individuals. This study aimed to evaluate the effects of physical activity (PA) on free fatty acid (FFA) levels, IR, and BP in obese older women. METHODS Twenty-three participants were randomly assigned to either the control group (CON, n = 11) or the physical activity group (PA, n = 12). The PA group was provided with a target of achieving >7,000 steps/day for 5 days each week. Body composition, FFA levels, IR, and BP were measured at pre- and post- of the 12-week intervention. RESULTS The analysis revealed a statistically significant interaction between FFA (p < 0.01), IR (p < 0.01), and SBP (p < 0.001). FFA (p < 0.5), IR (p < 0.5), and systolic blood pressure (SBP) (p < 0.01) were significantly decreased in the PA group compared to those in the CON group, which showed no significant changes in FFA, IR, and SBP. CONCLUSION PA significantly decreased FFA, IR, and SBP in older women with obesity. Therefore, PA is an effective intervention for the prevention and management of obesity and cardiovascular diseases in obese older women.
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Affiliation(s)
- Woo-Hyeon Son
- Institute of Convergence Bio-Health, Dong-A University, Busan, Republic of Korea
| | - Min-Seong Ha
- Laboratory of Sports Conditioning: Nutrition Biochemistry and Neuroscience, Department of Sport, College of the Arts and Sports, University of Seoul, Seoul, Republic of Korea
| | - Tae-Jin Park
- Department of Sports Healthcare, College of Humanities & Social Sciences, Inje University, Gimhae, Republic of Korea
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12
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Jabbar Al‐Rikabi S, Etemadi A, Morad M, Nowrouzi A, Panahi G, Mondeali M, Toorani‐ghazvini M, Nasli‐Esfahani E, Razi F, Bandarian F. Metabolomics Signature in Prediabetes and Diabetes: Insights From Tandem Mass Spectrometry Analysis. Endocrinol Diabetes Metab 2024; 7:e00484. [PMID: 38739122 PMCID: PMC11090150 DOI: 10.1002/edm2.484] [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: 02/16/2024] [Accepted: 04/01/2024] [Indexed: 05/14/2024] Open
Abstract
OBJECTIVE This study investigates the metabolic differences between normal, prediabetic and diabetic patients with good and poor glycaemic control (GGC and PGC). DESIGN In this study, 1102 individuals were included, and 50 metabolites were analysed using tandem mass spectrometry. The diabetes diagnosis and treatment standards of the American Diabetes Association (ADA) were used to classify patients. METHODS The nearest neighbour method was used to match controls and cases in each group on the basis of age, sex and BMI. Factor analysis was used to reduce the number of variables and find influential underlying factors. Finally, Pearson's correlation coefficient was used to check the correlation between both glucose and HbAc1 as independent factors with binary classes. RESULTS Amino acids such as glycine, serine and proline, and acylcarnitines (AcylCs) such as C16 and C18 showed significant differences between the prediabetes and normal groups. Additionally, several metabolites, including C0, C5, C8 and C16, showed significant differences between the diabetes and normal groups. Moreover, the study found that several metabolites significantly differed between the GGC and PGC diabetes groups, such as C2, C6, C10, C16 and C18. The correlation analysis revealed that glucose and HbA1c levels significantly correlated with several metabolites, including glycine, serine and C16, in both the prediabetes and diabetes groups. Additionally, the correlation analysis showed that HbA1c significantly correlated with several metabolites, such as C2, C5 and C18, in the controlled and uncontrolled diabetes groups. CONCLUSIONS These findings could help identify new biomarkers or underlying markers for the early detection and management of diabetes.
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Affiliation(s)
| | - Ali Etemadi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
- Medical Biotechnology Department, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
| | - Maher Mohammed Morad
- Department of Clinical Biochemistry, School of MedicineTehran University of Medical SciencesTehranIran
| | - Azin Nowrouzi
- Department of Clinical Biochemistry, School of MedicineTehran University of Medical SciencesTehranIran
| | | | - Mozhgan Mondeali
- Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
| | - Mahsa Toorani‐ghazvini
- Medical Biotechnology Department, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
| | - Ensieh Nasli‐Esfahani
- Diabetes Research CenterEndocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical SciencesTehranIran
| | - Farideh Razi
- Metabolomics and Genomics Research CenterEndocrinology and Metabolism Molecular‐Cellular Sciences Institute, Tehran University of Medical SciencesTehranIran
| | - Fatemeh Bandarian
- Metabolomics and Genomics Research CenterEndocrinology and Metabolism Molecular‐Cellular Sciences Institute, Tehran University of Medical SciencesTehranIran
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Salau VF, Erukainure OL, Olofinsan KO, Msomi NZ, Ijomone OM, Islam MS. Vanillin improves glucose homeostasis and modulates metabolic activities linked to type 2 diabetes in fructose-streptozotocin induced diabetic rats. Arch Physiol Biochem 2024; 130:169-182. [PMID: 34752171 DOI: 10.1080/13813455.2021.1988981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/29/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE This study investigated the antidiabetic effect of vanillin using in vitro, in silico, and in vivo experimental models. METHODOLOGY Type 2 diabetes (T2D) was induced in male Sprague-Dawley (SD) rats using fructose-streptozotocin (STZ), then orally administered low (150 mg/kg bodyweight) or high (300 mg/kg bodyweight) dose of vanillin for 5 weeks intervention period. RESULTS Vanillin suppressed the levels of blood glucose, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, uric acid, when elevated serum insulin, HDL-cholesterol, and concomitantly improved pancreatic β-cell function, glucose tolerance, and pancreatic morphology. It also elevated both serum and pancreatic tissue GSH level, SOD and catalase activities, and hepatic glycogen level, while depleting malondialdehyde level, α-amylase, lipase, acetylcholinesterase, ATPase, ENTPDase and 5'-nucleotidase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase activities. CONCLUSIONS The results indicate the potent antidiabetic effect of vanillin against T2D and its associated complications.
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Affiliation(s)
- Veronica F Salau
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Department of Biochemistry, Veritas University, Abuja, Nigeria
| | - Ochuko L Erukainure
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Department of Pharmacology, University of the Free State, Bloemfontein, South Africa
| | - Kolawole O Olofinsan
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Nontokozo Z Msomi
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
| | | | - Md Shahidul Islam
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
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14
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Liaghatdar A, Mazaheri-Tehrani S, Fakhrolmobasheri M. Management of Hypertension in Patients With Polycystic Ovarian Syndrome: A Mini-Review. Cardiol Rev 2024:00045415-990000000-00199. [PMID: 38305409 DOI: 10.1097/crd.0000000000000635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Polycystic ovarian syndrome (PCOS) is a common problem among young women. It is characterized mainly by hyperandrogenism features, such as hirsutism, menstrual problems, and anovulation. Diagnosis is based on the existence of 2 items out of, oligo-ovulation, hyperandrogenism features, and ultrasounds findings. Cardiovascular complications such as hypertension are a prevalent serious condition in these patients which is mainly predisposed by the high levels of androgens, and insulin resistance. High blood pressure should be controlled well to prevent the progression of other serious conditions. Various antihypertensive drugs could be prescribed. However, in selecting an antihypertensive medication, other therapeutic properties of the drug should also be considered. Up to now, many clinicians do not differ between PCOS patients with hypertension and other hypertensive patients. However, being aware of the potential effects of each hypertension drug could help to choose better options for the patient. Here is a brief review of how each antihypertensive drug could affect PCOS women and if they cause any improvement in the disorder progression.
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Affiliation(s)
- Amin Liaghatdar
- From the Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sadegh Mazaheri-Tehrani
- From the Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
- Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Fakhrolmobasheri
- From the Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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15
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Kueck PJ, Morris JK, Stanford JA. Current Perspectives: Obesity and Neurodegeneration - Links and Risks. Degener Neurol Neuromuscul Dis 2023; 13:111-129. [PMID: 38196559 PMCID: PMC10774290 DOI: 10.2147/dnnd.s388579] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024] Open
Abstract
Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.
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Affiliation(s)
- Paul J Kueck
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
| | - Jill K Morris
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA
| | - John A Stanford
- University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Landon Center on Aging, University of Kansas Medical Center, Kansas City, KS, 66160, USA
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Umbayev B, Saliev T, Safarova (Yantsen) Y, Yermekova A, Olzhayev F, Bulanin D, Tsoy A, Askarova S. The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity. Nutrients 2023; 15:4964. [PMID: 38068822 PMCID: PMC10707920 DOI: 10.3390/nu15234964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/22/2023] [Accepted: 11/26/2023] [Indexed: 12/18/2023] Open
Abstract
Age-related obesity significantly increases the risk of chronic diseases such as type 2 diabetes, cardiovascular diseases, hypertension, and certain cancers. The insulin-leptin axis is crucial in understanding metabolic disturbances associated with age-related obesity. Rho GTPase Cdc42 is a member of the Rho family of GTPases that participates in many cellular processes including, but not limited to, regulation of actin cytoskeleton, vesicle trafficking, cell polarity, morphology, proliferation, motility, and migration. Cdc42 functions as an integral part of regulating insulin secretion and aging. Some novel roles for Cdc42 have also been recently identified in maintaining glucose metabolism, where Cdc42 is involved in controlling blood glucose levels in metabolically active tissues, including skeletal muscle, adipose tissue, pancreas, etc., which puts this protein in line with other critical regulators of glucose metabolism. Importantly, Cdc42 plays a vital role in cellular processes associated with the insulin and leptin signaling pathways, which are integral elements involved in obesity development if misregulated. Additionally, a change in Cdc42 activity may affect senescence, thus contributing to disorders associated with aging. This review explores the complex relationships among age-associated obesity, the insulin-leptin axis, and the Cdc42 signaling pathway. This article sheds light on the vast molecular web that supports metabolic dysregulation in aging people. In addition, it also discusses the potential therapeutic implications of the Cdc42 pathway to mitigate obesity since some new data suggest that inhibition of Cdc42 using antidiabetic drugs or antioxidants may promote weight loss in overweight or obese patients.
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Affiliation(s)
- Bauyrzhan Umbayev
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
| | - Timur Saliev
- S.D. Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan;
| | - Yuliya Safarova (Yantsen)
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
| | - Aislu Yermekova
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
| | - Farkhad Olzhayev
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
| | - Denis Bulanin
- Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan;
| | - Andrey Tsoy
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
| | - Sholpan Askarova
- National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan; (Y.S.); (A.Y.); (F.O.); (A.T.); (S.A.)
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Jain N, Patel B, Hanawal M, Lila AR, Memon S, Bandgar T, Kumar A. Machine learning for predicting diabetic metabolism in the Indian population using polar metabolomic and lipidomic features. Metabolomics 2023; 20:1. [PMID: 38017183 DOI: 10.1007/s11306-023-02066-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/16/2023] [Indexed: 11/30/2023]
Abstract
AIMS To identify metabolite and lipid biomarkers of diabetes in the Indian subpopulation in newly diagnosed diabetic and long-term diabetic individuals. To utilize the global polar metabolomic and lipidomic profiles to predict the susceptibility of an individual to diabetes using machine learning algorithms. MATERIALS AND METHODS 87 individuals, including healthy, newly diabetic, and long-term diabetics on medication, were included in the study. Post consent, their serum was used to isolate polar metabolome and lipidome. NMR and LCMS were used to identify the polar metabolites and lipids, respectively. Statistical analysis was done to determine significantly altered molecules. NMR and LCMS comprehensive data were utilized to generate diabetic models using machine learning algorithms. 10 more individuals (pre-diabetic) were recruited, and their polar metabolomic and lipidomic profiles were generated. Pre-diabetic metabolic profiles were then utilized to predict the diabetic status of the metabolome and lipidome beyond glucose levels. RESULTS Mannose, Betaine, Xanthine, Triglyceride (38:1), Sphingomyelin (d63:7), and Phosphatidic acid (37:2) are some of the top key biomarkers of diabetes. The predictive model generated showed the receiver operating characteristic area under the curve (ROC-AUC) as 1 on both test and validation data indicating excellent accuracy. This model then predicted the diabetic closeness of the metabolism of pre-diabetic individuals based on probability scores. CONCLUSION Polar metabolic and lipid profile of diabetic individuals is very different from that of healthy individuals. Lipid profile alters before the polar metabolic profile in diabetes-susceptible individuals. Without regard to glucose, the diabetic closeness of the metabolism of any individual can be determined.
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Affiliation(s)
- Nikita Jain
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India
| | - Bhaumik Patel
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India
| | - Manjesh Hanawal
- Industrial Engineering and Operations Research, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India
| | - Anurag R Lila
- Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, 400012, India
| | - Saba Memon
- Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, 400012, India
| | - Tushar Bandgar
- Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, 400012, India
| | - Ashutosh Kumar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India.
- Lab No. 606, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Bombay, Mumbai, 400076, India.
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18
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Tajiri E, Yoshimura E, Tobina T, Yamashita T, Kume K, Hatamoto Y, Shimoda S. Effects of sleep restriction on food intake and appetite under free-living conditions: A randomized crossover trial. Appetite 2023; 189:106998. [PMID: 37562755 DOI: 10.1016/j.appet.2023.106998] [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: 04/27/2023] [Revised: 08/03/2023] [Accepted: 08/07/2023] [Indexed: 08/12/2023]
Abstract
To investigate changes in subjective psychological factors and dietary intake during sleep restriction, we carried out a randomized crossover trial with a 3-day sleep restriction condition (SR; 5 h of sleep) and control sleep condition (CS; 8 h of sleep). Days 3 and 4 involved free-living and laboratory (in the morning) conditions, respectively. Subjective psychological factors (hunger, appetite, desire for sweets and fatty foods, sleepiness, and fatigue) were assessed using a 0.0-10.0 cm visual analog scale (VAS) every hour throughout the day on day 3, and at 8:00 a.m. on day 4. Dietary intake on day 3 was assessed on the basis of the food purchased and eaten. Fasting blood samples were collected at 8:00 a.m. on day 4. Dietary intake during the ad libitum breakfast was assessed on day 4. The participants were 13 women and 11 men (mean age, 21.4 ± 1.0 years; mean body mass index, 19.8 ± 1.7 kg/m2). The areas under the curve 0-16 h after waking for hunger, desire for fatty foods, sleepiness, and fatigue were higher in the SR than CS on day 3 (P < 0.05). Energy and carbohydrate intakes from snacks (daytime and nighttime) on day 3 were higher in the SR than CS (P < 0.05) but total dietary intake on day 3 was not different between the conditions (P > 0.05). The 2-arachidonoylglycerol level was different between the conditions (P < 0.05), but was not associated with sweet taste preference, dietary intake, or the active ghrelin level on day 4 (P > 0.05). In conclusion, ratings for subjective psychological factors and energy and carbohydrate intakes from snacks increased in association with sleep restriction under free-living conditions.
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Affiliation(s)
- Eri Tajiri
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto, 862-8502, Japan.
| | - Eiichi Yoshimura
- Department of Nutrition and Metabolism, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 566-0002, Japan.
| | - Takuro Tobina
- Faculty of Nursing and Nutrition, University of Nagasaki, Nagasaki, 851-2195, Japan.
| | - Tomoki Yamashita
- Faculty of Nursing and Nutrition, University of Nagasaki, Nagasaki, 851-2195, Japan.
| | - Kokoro Kume
- Faculty of Nursing and Nutrition, University of Nagasaki, Nagasaki, 851-2195, Japan.
| | - Yoichi Hatamoto
- Department of Nutrition and Metabolism, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 566-0002, Japan.
| | - Seiya Shimoda
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto, 862-8502, Japan.
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Luo H, Zhu Z. Serum acylcarnitines levels as a potential predictor for gestational diabetes: a systematic review and meta-analysis. Front Public Health 2023; 11:1217237. [PMID: 37469690 PMCID: PMC10352491 DOI: 10.3389/fpubh.2023.1217237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 06/19/2023] [Indexed: 07/21/2023] Open
Abstract
Aims Gestational diabetes mellitus (GDM) stands as a prevalent obstetric complication bearing consequential health implications for both mother and child. While existing studies have probed the alterations in acylcarnitines during GDM, an updated systematic meta-analysis is needed to consolidate these findings. Hence, this study endeavours to furnish a comprehensive systematic review and meta-analysis delineating the association between acylcarnitines and GDM, aimed at bolstering diagnostic accuracy and preventive measures against GDM. Methods To extract pertinent studies for this meta-analysis, we meticulously scoured databases such as PubMed, Web of Science, Embase, and Cochrane Library up until May 2023. The inclusion criteria were studies contrasting plasma metabolomics between two cohorts: women diagnosed with GDM and normoglycemic pregnant women. Weighted mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using random-effects models. The I2 index was employed to quantify heterogeneity amongst the studies. All meta-analyses were executed using Stata version 12.0. Results Our meta-analysis included eight studies encompassing 878 pregnant women. The analysis disclosed that relative to normoglycemic pregnant women, women with GDM exhibited significantly elevated levels of Short-Chain Acylcarnitines (SCAC) (SMD: 0.19, 95% CI: 0.02-0.36, I2 = 71.3%). No substantial difference was discerned in fasting total carnitine levels (SMD: 0.15, 95% CI: -0.16-0.31, I2 = 68.2%), medium-chain acylcarnitines (MCAC) (SMD: 0.08, 95% CI: -0.02-0.36, I2 = 79.0%), and long-chain acylcarnitines (LCAC) (SMD: 0.04, 95% CI: -0.06-0.15, I2 = 0%). Neither funnel plot assessment nor Egger's regression and Begg's rank correlation tests indicated any evidence of publication bias. Conclusion Our meta-analysis suggests that elevated levels of SCAC may heighten the risk of GDM onset. Given GDM's deleterious impact on pregnant women and their offspring, these findings underscore the clinical imperative of managing this condition. Early surveillance of plasma metabolomic profiles, particularly serum acylcarnitine concentrations, may equip clinicians with a valuable tool for timely diagnosis and intervention in GDM.
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Affiliation(s)
- Hairong Luo
- National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zanlei Zhu
- Department of Respiratory and Critical Care Medicine, Ganzhou People’s Hospital (Ganzhou Hospital Affiliated to Nanchang University/Nanfang Medical University), Ganzhou, Jiangxi Province, China
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20
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Bisht MK, Dahiya P, Ghosh S, Mukhopadhyay S. The cause-effect relation of tuberculosis on incidence of diabetes mellitus. Front Cell Infect Microbiol 2023; 13:1134036. [PMID: 37434784 PMCID: PMC10330781 DOI: 10.3389/fcimb.2023.1134036] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 05/25/2023] [Indexed: 07/13/2023] Open
Abstract
Tuberculosis (TB) is one of the oldest human diseases and is one of the major causes of mortality and morbidity across the Globe. Mycobacterium tuberculosis (Mtb), the causal agent of TB is one of the most successful pathogens known to mankind. Malnutrition, smoking, co-infection with other pathogens like human immunodeficiency virus (HIV), or conditions like diabetes further aggravate the tuberculosis pathogenesis. The association between type 2 diabetes mellitus (DM) and tuberculosis is well known and the immune-metabolic changes during diabetes are known to cause increased susceptibility to tuberculosis. Many epidemiological studies suggest the occurrence of hyperglycemia during active TB leading to impaired glucose tolerance and insulin resistance. However, the mechanisms underlying these effects is not well understood. In this review, we have described possible causal factors like inflammation, host metabolic changes triggered by tuberculosis that could contribute to the development of insulin resistance and type 2 diabetes. We have also discussed therapeutic management of type 2 diabetes during TB, which may help in designing future strategies to cope with TB-DM cases.
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Affiliation(s)
- Manoj Kumar Bisht
- Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
- Regional Centre for Biotechnology, Faridabad, India
| | - Priyanka Dahiya
- Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
- Regional Centre for Biotechnology, Faridabad, India
| | - Sudip Ghosh
- Molecular Biology Unit, Indian Council of Medical Research (ICMR)-National Institute of Nutrition, Jamai Osmania PO, Hyderabad, India
| | - Sangita Mukhopadhyay
- Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
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21
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Ciarambino T, Crispino P, Leto G, Minervini G, Para O, Giordano M. Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives. Int J Mol Sci 2023; 24:10409. [PMID: 37373556 DOI: 10.3390/ijms241210409] [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: 05/22/2023] [Revised: 06/12/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.
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Affiliation(s)
- Tiziana Ciarambino
- Internal Medicine Department, Hospital of Marcianise, ASL Caserta, 81037 Caserta, Italy
| | - Pietro Crispino
- Internal Medicine Department, Hospital of Latina, ASL Latina, 04100 Latina, Italy
| | - Gaetano Leto
- Department of Experimental Medicine, University La Sapienza Roma, 00185 Rome, Italy
| | - Giovanni Minervini
- Internal Medicine Department, Hospital of Lagonegro, AOR San Carlo, 85042 Lagonegro, Italy
| | - Ombretta Para
- Internal Emergency Department, Hospital of Careggi, University of Florence, 50121 Florence, Italy
| | - Mauro Giordano
- Department of Medical Science, University of Campania, L. Vanvitelli, 81100 Naples, Italy
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Liu FS, Wang S, Guo XS, Ye ZX, Zhang HY, Li Z. State of art on the mechanisms of laparoscopic sleeve gastrectomy in treating type 2 diabetes mellitus. World J Diabetes 2023; 14:632-655. [PMID: 37383590 PMCID: PMC10294061 DOI: 10.4239/wjd.v14.i6.632] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 04/01/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Obesity and type-2 diabetes mellitus (T2DM) are metabolic disorders. Obesity increases the risk of T2DM, and as obesity is becoming increasingly common, more individuals suffer from T2DM, which poses a considerable burden on health systems. Traditionally, pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and all-cause mortality and to increase life expectancy. Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity, especially in patients with refractory obesity, owing to its many benefits including good long-term outcomes and almost no weight regain. The bariatric surgery options have markedly changed recently, and laparoscopic sleeve gastrectomy (LSG) is gradually gaining popularity. LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity, with a high cost-benefit ratio. Here, we review the me-chanism associated with LSG treatment of T2DM, and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones, gut microbiota, bile acids, and adipokines to clarify current treatment modalities for patients with obesity and T2DM.
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Affiliation(s)
- Fa-Shun Liu
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Song Wang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Xian-Shan Guo
- Department of Endocrinology, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
| | - Zhen-Xiong Ye
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Hong-Ya Zhang
- Central Laboratory, Yangpu District Control and Prevention Center, Shanghai 200090, China
| | - Zhen Li
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
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Zhou J, Shi Y, Yang C, Lu S, Zhao L, Liu X, Zhou D, Luo L, Yin Z. γ-glutamylcysteine alleviates insulin resistance and hepatic steatosis by regulating adenylate cyclase and IGF-1R/IRS1/PI3K/Akt signaling pathways. J Nutr Biochem 2023:109404. [PMID: 37311491 DOI: 10.1016/j.jnutbio.2023.109404] [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: 03/29/2023] [Revised: 06/02/2023] [Accepted: 06/07/2023] [Indexed: 06/15/2023]
Abstract
Type 2 diabetes mellitus (T2DM), a complex metabolism disease, which was characterized by metabolic disorders including hyperglycemia, has become a major health problem due to the increasing prevalence worldwide. γ-glutamylcysteine (γ-GC) as an immediate precursor of glutathione (GSH) was originally used for the treatment of sepsis, inflammation bowel disease, and senescence. Here, we evaluated the capacity of γ-GC on diabetes-related metabolic parameters in db/db mice and insulin resistance (IR) amelioration in cells induced by palmitic acid (PA). Our data suggested that γ-GC treatment decreased body weight, reduced adipose tissue size, ameliorated ectopic fat deposition in liver, increased the GSH content in liver, improved glucose control and other diabetes-related metabolic parameters in vivo. Moreover, in vitro experiments showed that γ-GC could maintain the balance of free fatty acids (FFAs) and glucose uptake through regulating the translocation of CD36 and GLUT4 from cytoplasm to plasma membrane. Furthermore, our finding also provided evidence that γ-GC could activate Akt not only via adenylate cyclase (AC)/cAMP/PI3K signaling pathway, but also via IGF-1R/IRS1/PI3K signaling pathway to improve IR and hepatic steatosis. Blocking either of two signaling pathways could not activate Akt activation induced by γ-GC. This unique characteristic ensures the important role of γ-GC in glucose metabolism. Collectively, these results suggested that γ-GC could serve as a candidate dipeptide for the treatment of T2DM and related chronic diabetic complications via activating AC and IGF-1R/IRS1/PI3K/Akt signaling pathways to regulate CD36 and GLUT4 trafficking.
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Affiliation(s)
- Jinyi Zhou
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Yingying Shi
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Chen Yang
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Shuai Lu
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Lishuang Zhao
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Xianli Liu
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China
| | - Da Zhou
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
| | - Lan Luo
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
| | - Zhimin Yin
- Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
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Naomi R, Teoh SH, Rusli RNM, Embong H, Bahari H, Kumar J. Elateriospermum tapos Yoghurt as a Therapeutic Intervention for Obesity-Associated Cognitive Impairments and Anxiety-like Behaviour in a High Fat Diet Maternal Obese Rat Model. Nutrients 2023; 15:nu15102312. [PMID: 37242195 DOI: 10.3390/nu15102312] [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] [Received: 04/18/2023] [Revised: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
Maternal obesity can be considered an intergenerational cycle and is also an important indicator of cognitive impairments. It is thought that using natural products is the best and safest way to combat maternal obesity and associated complications. Recent studies have shown that Elateriospermum tapos (E. tapos) contains bioactive compounds with anti-obesity effects, and yoghurt is a convenient medium for supplementing obese maternal rats with E. tapos extract. Thus, the aim of this study is to investigate the impact of E. tapos in yoghurt on maternally obese rats' cognitive function supplemented with a high-fat diet (HFD). In this study, 48 female Sprague-Dawley rats were used. The rats were fed HFD for a period of 16 weeks to induce obesity, after which they were allowed to mate. Upon confirmation of pregnancy, obese rats were given varying doses of E. tapos (5, 50, and 500 mg/kg) in yoghurt until postnatal (PND) day 21. On PND 21, the dams' body mass index (BMI), Lee index, abdominal circumference, oxidative status, and metabolic profile were measured. The behavioral tests (open field, place, and object recognition) were conducted on PND 21 to access memory. The results show that the 50 and 500 mg/kg E. tapos in yoghurt supplemented groups had similar BMI, Lee index, abdominal circumference, lipid profile, FBG, insulin, FRAP, and GSH levels, as well as a similar recognition index, in comparison with the control group supplemented with saline. In conclusion, the results of this study indicate that the newly formulated E. tapos in yogurt can act as an anti-obesity agent in maternal obesity, alleviate anxiety, and enhance hippocampal-dependent memory.
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Affiliation(s)
- Ruth Naomi
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Soo Huat Teoh
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia
| | - Rusydatul Nabila Mahmad Rusli
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Hashim Embong
- Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Hasnah Bahari
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Jaya Kumar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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Gao SY, Liu YP, Wen R, Huang XM, Li P, Yang YH, Yang N, Zhang TN. Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy. FASEB J 2023; 37:e22866. [PMID: 36929614 DOI: 10.1096/fj.202201397rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 02/10/2023] [Accepted: 02/27/2023] [Indexed: 03/18/2023]
Abstract
Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
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Affiliation(s)
- Shan-Yan Gao
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yong-Ping Liu
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ri Wen
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xin-Mei Huang
- Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Ping Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hang Yang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ni Yang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tie-Ning Zhang
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
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Wang C, Li X, Zhang W, Liu W, Lv Z, Gui R, Li M, Li Y, Sun X, Liu P, Fan X, Yang S, Xiong Y, Qian L. ETNPPL impairs autophagy through regulation of the ARG2-ROS signaling axis, contributing to palmitic acid-induced hepatic insulin resistance. Free Radic Biol Med 2023; 199:126-140. [PMID: 36841363 DOI: 10.1016/j.freeradbiomed.2023.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 02/12/2023] [Accepted: 02/21/2023] [Indexed: 02/27/2023]
Abstract
Excessive free fatty acids (FFAs) accumulation is a leading risk factor for the pathogenesis of insulin resistance (IR) in metabolic tissues, including the liver. Ethanolamine-phosphate phospho-lyase (ETNPPL), a newly identified metabolic enzyme, catalyzes phosphoethanolamine (PEA) to ammonia, inorganic phosphate, and acetaldehyde and is highly expressed in hepatic tissue. Whether it plays a role in regulating FFA-induced IR in hepatocytes has yet to be understood. In this study, we established an in vitro palmitic acid (PA)-induced IR model in human HepG2 cells and mouse AML12 cells with chronic treatment of PA. Next, we overexpressed ETNPPL by using lentivirus-mediated ectopic to investigate the effects of ETNPPL per se on IR without PA stimulation. We show that ETNPPL expression is significantly elevated in PA-induced IR and that silencing ETNPPL ameliorates this IR in hepatocytes. Inversely, overexpressing ETNPPL under normal conditions without PA promotes IR, reactive oxygen species generation, and ARG2 activation in both HepG2 and AML12 cells. Moreover, ETNPPL depletion markedly down-regulates ARG2 expression in hepatocytes. Besides, silencing ARG2 prevents ETNPPL-induced ROS accumulation and inhibition of autophagic flux and IR in hepatocytes. Finally, we found that phytopharmaceutical disruption of ETNPPL by quercetin ameliorates PA-induced IR in hepatocytes. Our study discloses that ETNPPL inhibiting autophagic flux mediates insulin resistance triggered by PA in hepatocytes via ARG2/ROS signaling cascade. Our findings provide novel insights into elucidating the pathogenesis of obesity-associated hepatic IR, suggesting that targeting ETNPPL might represent a potential approach for T2DM therapy.
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Affiliation(s)
- Caihua Wang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Xiaofang Li
- Department of Gastroenterology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Wei Zhang
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Wenxuan Liu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Ziwei Lv
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Runlin Gui
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Man Li
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Yujia Li
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Xiaomin Sun
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Ping Liu
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Xiaobin Fan
- Department of Obstetrics and Gynecology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Shiyao Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China
| | - Yuyan Xiong
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China.
| | - Lu Qian
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710069, PR China; Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, 710018, PR China.
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Zhang X, Yun Y, Lai Z, Ji S, Yu G, Xie Z, Zhang H, Zhong X, Wang T, Zhang L. Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets. J Anim Sci Biotechnol 2023; 14:36. [PMID: 36907895 PMCID: PMC10009951 DOI: 10.1186/s40104-023-00828-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 01/03/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND Intrauterine growth restriction (IUGR) can cause lipid disorders in infants and have long-term adverse effects on their growth and development. Clostridium butyricum (C. butyricum), a kind of emerging probiotics, has been reported to effectively attenuate lipid metabolism dysfunctions. Therefore, the objective of this study was to investigate the effects of C. butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets. METHODS Sixteen IUGR and eight normal birth weight (NBW) neonatal male piglets were used in this study. From d 3 to d 24, in addition to drinking milk, the eight NBW piglets (NBW-CON group, n = 8) and eight IUGR piglets (IUGR-CON group, n = 8) were given 10 mL sterile saline once a day, while the remaining IUGR piglets (IUGR-CB group, n = 8) were orally administered C. butyricum at a dose of 2 × 108 colony-forming units (CFU)/kg body weight (suspended in 10 mL sterile saline) at the same frequency. RESULTS The IUGR-CON piglets exhibited restricted growth, impaired hepatic morphology, disordered lipid metabolism, increased abundance of opportunistic pathogens and altered ileum and liver bile acid (BA) profiles. However, C. butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets, characterized by a decreased abundance of opportunistic pathogens in the ileum, including Streptococcus and Enterococcus. The decrease in these bile salt hydrolase (BSH)-producing microbes increased the content of conjugated BAs, which could be transported to the liver and function as signaling molecules to activate liver X receptor α (LXRα) and farnesoid X receptor (FXR). This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol. As a result, the growth performance and morphological structure of the liver improved in the IUGR piglets. CONCLUSION These results indicate that C. butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes (Streptococcus and Enterococcus). This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRα and FXR. The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.
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Affiliation(s)
- Xin Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Yang Yun
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Zheng Lai
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Shuli Ji
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Ge Yu
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Zechen Xie
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Hao Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Xiang Zhong
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Tian Wang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Lili Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China.
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Zhou R, He D, Zhang H, Xie J, Zhang S, Tian X, Zeng H, Qin Y, Huang L. Ginsenoside Rb1 protects against diabetes-associated metabolic disorders in Kkay mice by reshaping gut microbiota and fecal metabolic profiles. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:115997. [PMID: 36509256 DOI: 10.1016/j.jep.2022.115997] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 11/14/2022] [Accepted: 11/25/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Panax quinquefolius Linn. is one of the most valuable herbal medicine in the world for its broad health benefits, including anti-diabetes. Ginsenoside Rb1, the principal active constituent of Panax quinquefolius Linn., could attenuate insulin resistance and metabolic disorders. The dysfunction of gut microbiota and fecal metabolites plays an important role in the pathogenesis of Type 2 Diabetes mellitus (T2DM). However, whether ginsenoside Rb1's hypoglycemic effect is related to gut microbiota remains elusive. AIM OF THE STUDY Our study aimed to explore the insulin-sensitizing and anti-diabetic effects of ginsenoside Rb1 as well as the underlying mechanisms. MATERIALS AND METHODS The T2DM model were established by high fat diet (HFD)-induced Kkay mice. The anti-diabetic effect of ginsenoside Rb1 (200 mg/kg/day) was evaluated by random blood glucose (RBG), fasting blood glucose (FBG), glucose tolerance test (OGTT), serum insulin level, insulin resistance index (HOMA-IR), pancreatic histology analysis, liver indexes, total triglyceride (TG) and total cholesterol (TC). Subsequently, 16S rRNA sequencing and LC-MS-based untargeted metabolomics were applied to characterize the microbiome and metabolites profile in HFD-induced Kkay mice, respectively. Finally, antibiotic treatment was used to validate the potential mechanism of ginsenoside Rb1 by modulating gut microbiota. RESULTS Our results showed that ginsenoside Rb1 reduced blood glucose, OGTT, serum insulin level, HOMA-IR, liver indexes as well as pancreatic injury. In addition, the ginsenoside Rb1 reversed the gut microbiota dysbiosis in diabetic Kkay mice, as indicated by the elevated abundance of Parasutterella, decreased population of Alistipes, f_Prevotellaceae_unclassified, Odoribacter, Anaeroplasma. Moreover, ginsenoside Rb1 altered free fatty acid (FFA) levels in fecal metabolites, such as decreased the level of α-linolenic acid, 13-OxoODE, oleic acid, 13-HODE, arachidonic acid, palmitic acid, stearic acid, while increased the level of PC (14:0/22:1(13Z)) and PC (16:0/16:0). Notably, ginsenoside Rb1 failed to improve HFD-induced diabetes in Kkay mice with antibiotics intervention. CONCLUSION These findings suggested that ginsenoside Rb1 may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play essential roles in diabetes-associated metabolic disorders and insulin resistance.
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Affiliation(s)
- Rongrong Zhou
- The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, China
| | - Dan He
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China; Hunan University of Chinese Medicine, Changsha, PR China
| | - Haichao Zhang
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China; Hunan University of Chinese Medicine, Changsha, PR China
| | - Jing Xie
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China; Hunan University of Chinese Medicine, Changsha, PR China
| | - Shuihan Zhang
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China
| | - Xuefei Tian
- Hunan University of Chinese Medicine, Changsha, PR China
| | - Hongliang Zeng
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China.
| | - Yuhui Qin
- Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China; Hunan University of Chinese Medicine, Changsha, PR China.
| | - Luqi Huang
- China Academy of Chinese Medical Sciences, Beijing, China.
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Martín-Saladich Q, Simó R, Aguadé-Bruix S, Simó-Servat O, Aparicio-Gómez C, Hernández C, Ramirez-Serra C, Pizzi MN, Roque A, González Ballester MA, Herance JR. Insights into Insulin Resistance and Calcification in the Myocardium in Type 2 Diabetes: A Coronary Artery Analysis. Int J Mol Sci 2023; 24:ijms24043250. [PMID: 36834662 PMCID: PMC9959651 DOI: 10.3390/ijms24043250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/27/2023] [Accepted: 02/01/2023] [Indexed: 02/10/2023] Open
Abstract
Type 2 diabetes (T2D) is responsible for high incidence of cardiovascular (CV) complications leading to heart failure. Coronary artery region-specific metabolic and structural assessment could provide deeper insight into the extent of the disease and help prevent adverse cardiac events. Therefore, in this study, we aimed at investigating such myocardial dynamics for the first time in insulin-sensitive (mIS) and insulin-resistant (mIR) T2D patients. We targeted global and region-specific variations using insulin sensitivity (IS) and coronary artery calcifications (CACs) as CV risk factor in T2D patients. IS was computed using myocardial segmentation approaches at both baseline and after an hyperglycemic-insulinemic clamp (HEC) on [18F]FDG-PET images using the standardized uptake value (SUV) (ΔSUV = SUVHEC - SUVBASELINE) and calcifications using CT Calcium Scoring. Results suggest that some communicating pathways between response to insulin and calcification are present in the myocardium, whilst differences between coronary arteries were only observed in the mIS cohort. Risk indicators were mostly observed for mIR and highly calcified subjects, which supports previously stated findings that exhibit a distinguished exposure depending on the impairment of response to insulin, while projecting added potential complications due to arterial obstruction. Moreover, a pattern relating calcification and T2D phenotypes was observed suggesting the avoidance of insulin treatment in mIS but its endorsement in mIR subjects. The right coronary artery displayed more ΔSUV, whilst plaque was more present in the circumflex. However, differences between phenotypes, and therefore CV risk, were associated to left descending artery (LAD) translating into higher CACs regarding IR, which could explain why insulin treatment was effective for LAD at the expense of higher likelihood of plaque accumulation. Personalized approaches to assess T2D may lead to more efficient treatments and risk-prevention strategies.
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Affiliation(s)
- Queralt Martín-Saladich
- Medical Molecular Imaging Research Group, Nuclear Medicine, Radiology and Cardiology Departments, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- BCN Medtech, Department of Information and Communication Technologies, Pompeu Fabra University, 08018 Barcelona, Spain
| | - Rafael Simó
- Diabetes and Metabolism Research Group, VHIR, Department of Endocrinology, Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Santiago Aguadé-Bruix
- Medical Molecular Imaging Research Group, Nuclear Medicine, Radiology and Cardiology Departments, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Group, VHIR, Department of Endocrinology, Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Carolina Aparicio-Gómez
- Medical Molecular Imaging Research Group, Nuclear Medicine, Radiology and Cardiology Departments, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Group, VHIR, Department of Endocrinology, Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Clara Ramirez-Serra
- Clinical Biochemistry Research Group, Vall d’Hebron Research Institute (VHIR), Biochemical Core Facilities, Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
| | - María Nazarena Pizzi
- Department of Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain
- Cardiology Department, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Albert Roque
- Medical Molecular Imaging Research Group, Nuclear Medicine, Radiology and Cardiology Departments, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain
- Radiology Department, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Miguel A. González Ballester
- BCN Medtech, Department of Information and Communication Technologies, Pompeu Fabra University, 08018 Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
- Correspondence: (M.A.G.B.); (J.R.H.); Tel.: +34-(93)-542-2000 (ext. 2083) (M.A.G.B.); +34-(93)-489-3000 (ext. 4946) (J.R.H.)
| | - José Raul Herance
- Medical Molecular Imaging Research Group, Nuclear Medicine, Radiology and Cardiology Departments, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (M.A.G.B.); (J.R.H.); Tel.: +34-(93)-542-2000 (ext. 2083) (M.A.G.B.); +34-(93)-489-3000 (ext. 4946) (J.R.H.)
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Saka SO, Salisu YY, Sahabi HM, Sanusi KO, Ibrahim KG, Abubakar MB, Isa SA, Liman MG, Shehu S, Malami I, Chan KW, Azmi NH, Imam MU. Nutrigenomic Effects of White Rice and Brown Rice on the Pathogenesis of Metabolic Disorders in a Fruit Fly Model. Molecules 2023; 28:532. [PMID: 36677591 PMCID: PMC9865196 DOI: 10.3390/molecules28020532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/24/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] Open
Abstract
Consumption of white rice (WR) has been shown to predispose individuals to metabolic disorders. However, brown rice (BR), which is relatively richer in bioactive compounds, possesses anti-glycaemic and antioxidant effects. In this study, fifteen cultivars of paddy rice that are predominantly consumed in North West Nigeria were analysed for their nutritional composition, bioactive contents and effects on metabolic outcomes in a fruit fly model. Gene expression analyses were conducted on the whole fly, targeting dPEPCK, dIRS, and dACC. The protein, carbohydrate, and fibre contents and bioactives of all BR cultivars were significantly different (p < 0.05) from the WR cultivars. Moreover, it was demonstrated that the glucose and trehalose levels were significantly higher (p < 0.05), while glycogen was significantly lower (p < 0.05) in the WR groups compared to the BR groups. Similarly, the expression of dACC and dPEPCK was upregulated, while that of dIRS was downregulated in the WR groups compared to the BR groups. Sex differences (p < 0.05) were observed in the WR groups in relation to the nutrigenomic effects. Our findings confirm metabolic perturbations in fruit flies following consumption of WR via distortion of insulin signalling and activation of glycogenolysis and gluconeogenesis. BR prevented these metabolic changes possibly due to its richer nutritional composition.
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Affiliation(s)
- Saheed Olanrewaju Saka
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Yusuf Yahaya Salisu
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Biochemistry and Molecular Biology, Faculty of Science, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Hauwa’u Muhammad Sahabi
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Biochemistry and Molecular Biology, Faculty of Science, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Kamaldeen Olalekan Sanusi
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Kasimu Ghandi Ibrahim
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Murtala Bello Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Suleiman Ahmed Isa
- Department of Biochemistry and Molecular Biology, Faculty of Science, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Muhammad Gidado Liman
- Department of Pure and Applied Chemistry, Faculty of Science, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Sha’aya’u Shehu
- Department of Biochemistry and Molecular Biology, Faculty of Science, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Ibrahim Malami
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
| | - Kim Wei Chan
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM, Serdang 43400, Selangor, Malaysia
| | - Nur Hanisah Azmi
- Faculty of Food Science and Nutrition, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Mustapha Umar Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2254, Nigeria
- Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria
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Yang C, Lu H, Li E, Oladele P, Ajuwon KM. Inulin supplementation induces expression of hypothalamic antioxidant defence genes in weaned piglets. J Anim Physiol Anim Nutr (Berl) 2023; 107:157-164. [PMID: 35253266 DOI: 10.1111/jpn.13698] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 01/10/2023]
Abstract
Fibre plays an important role in diluting dietary energy density. Fibre is also implicated in the regulation of appetite, perhaps through direct effects in the brain. However, there is little information on this effect in pigs. Therefore, this study was conducted to investigate the effect of fibre type in regulating the expression of genes involved in appetite control, inflammation and antioxidant defence in the hypothalamus of weaned piglets. A total of 64 Duroc × Landrace × Yorkshire barrows at 37 days old were blocked by body weight and allotted to two dietary treatments, supplementation with either 0.25% cellulose (Solka-Floc) or inulin (INU) for 28 days, after which animals were killed for analysis. Pigs fed INU had a tendency (p = 0.06) for reduced feed intake in the first week, although this effect disappeared in subsequent weeks. Pigs supplemented with INU had lower expression of dopamine (dopamine receptor D2), serotonin (5-hydroxytryptamine receptor 1B), free fatty acid (GPR43) and neuropeptide Y receptor Y2 receptors in the hypothalamus (p < 0.05). Expression of the tryptophan hydroxylase 2 gene in the hypothalamus also tended (p = 0.09) to be lower for pigs fed INU. The abundance of antioxidant defence genes, superoxide dismutase (SOD1) and catalase, were greater (p < 0.05) but that of a proinflammatory gene, interleukin 1β, was lower (p < 0.05) in the hypothalamus of pigs fed INU. Therefore, consumption of INU causes downregulation of inflammation in the hypothalamus and regulation of the abundance of serotonin or dopamine receptors, and may also increase antioxidant defence through upregulation of SOD and catalase in weaned piglets.
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Affiliation(s)
- Can Yang
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA.,College of Life Sciences and Environment, Hengyang Normal University, Hengyang, Hunan, China.,Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Hunan Normal University, Changsha, Hunan, China
| | - Hang Lu
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA
| | - Enkai Li
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA
| | - Paul Oladele
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA
| | - Kolapo M Ajuwon
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA
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Liang K, Dai JY. Progress of potential drugs targeted in lipid metabolism research. Front Pharmacol 2022; 13:1067652. [PMID: 36588702 PMCID: PMC9800514 DOI: 10.3389/fphar.2022.1067652] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022] Open
Abstract
Lipids are a class of complex hydrophobic molecules derived from fatty acids that not only form the structural basis of biological membranes but also regulate metabolism and maintain energy balance. The role of lipids in obesity and other metabolic diseases has recently received much attention, making lipid metabolism one of the attractive research areas. Several metabolic diseases are linked to lipid metabolism, including diabetes, obesity, and atherosclerosis. Additionally, lipid metabolism contributes to the rapid growth of cancer cells as abnormal lipid synthesis or uptake enhances the growth of cancer cells. This review introduces the potential drug targets in lipid metabolism and summarizes the important potential drug targets with recent research progress on the corresponding small molecule inhibitor drugs. The significance of this review is to provide a reference for the clinical treatment of metabolic diseases related to lipid metabolism and the treatment of tumors, hoping to deepen the understanding of lipid metabolism and health.
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Affiliation(s)
- Kai Liang
- School of Life Science, Peking University, Beijing, China,*Correspondence: Kai Liang, ; Jian-Ye Dai,
| | - Jian-Ye Dai
- School of Pharmacy, Lanzhou University, Lanzhou, China,Collaborative Innovation Center for Northwestern Chinese Medicine, Lanzhou University, Lanzhou, China,*Correspondence: Kai Liang, ; Jian-Ye Dai,
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Takahashi N, Sasaki A, Umemura A, Sugai T, Kakisaka K, Ishigaki Y. Identification of a Fatty Acid for Diagnosing Non-Alcoholic Steatohepatitis in Patients with Severe Obesity Undergoing Metabolic Surgery. Biomedicines 2022; 10:biomedicines10112920. [PMID: 36428489 PMCID: PMC9687903 DOI: 10.3390/biomedicines10112920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
The prevalence of nonalcoholic steatohepatitis (NASH) in severely obese Japanese patients is extremely high. However, there are currently no methods other than liver biopsy to assess hepatic steatosis and fibrosis. The purpose of this study was to comprehensively analyze changes in fatty acid (FA) and serum-free fatty acid (FFA) metabolism in severely obese Japanese patients to determine whether these could be surrogate markers. In this study, we enrolled 20 Japanese patients who underwent laparoscopic sleeve gastrectomy (LSG) for severe obesity and intraoperative liver biopsy. Serum FFAs were analyzed with liquid chromatography-mass spectrometry, and FAs in liver tissue were assessed using matrix-assisted laser desorption/ionization-imaging mass spectrometry to determine FAs that may be indicative of a positive NASH diagnosis. All patients showed significant weight loss and metabolic improvement following LSG. Regarding weight loss and metabolic improvement indices, 23 FFAs showed significant correlations with the baseline data. Narrowing down the phospholipids to commonly detected FAs detected in liver tissue, PC(18:1e_20:4) was significantly changed in the NASH group, suggesting that it could be used as a surrogate marker for NASH diagnosis. The results suggest that specific postoperative changes in blood phospholipids could be used as surrogate markers for NASH treatment.
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Affiliation(s)
- Naoto Takahashi
- Department of Surgery, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
| | - Akira Sasaki
- Department of Surgery, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
- Correspondence: ; Tel.: +81-19-6137111
| | - Akira Umemura
- Department of Surgery, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
| | - Tamotsu Sugai
- Division of Molecular Diagnostic Pathology, Department of Pathology, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
| | - Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
| | - Yasushi Ishigaki
- Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka 028-3695, Japan
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Hao Y, Qu L, Guo Y, Ma L, Guo M, Zhu Y, Jin Y, Gu Q, Zhang Y, Sun W. Association of pre-pregnancy low-carbohydrate diet with maternal oral glucose tolerance test levels in gestational diabetes. BMC Pregnancy Childbirth 2022; 22:734. [PMID: 36162989 PMCID: PMC9511732 DOI: 10.1186/s12884-022-05059-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 09/13/2022] [Indexed: 11/17/2022] Open
Abstract
Background Limited evidence exists on the correlation between the pre-pregnancy low-carbohydrate (LC) diet and maternal oral glucose tolerance test (OGTT) levels during pregnancy. Our aim was to compare the differences in maternal OGTT levels among women who had been diagnosed with gestational diabetes mellitus (GDM) during pregnancy and adopted different dietary patterns in the pre-pregnancy period. Methods A case–control study was conducted in 20 women with GDM who adhering to an LC diet (carbohydrate intake < 130 g/d) during pre-conception (LC/GDM,cases). Control subjects, who were matched in a 4:1 ratio, were 80 women with GDM and conventional diet (Con/GDM,control), and 80 women with conventional diet but without GDM (Con/Healthy,control). Women diagnosed with GDM using 75-g OGTT between 24 and 28 weeks of gestation. We used unadjusted raw data to compare the dietary composition data and biomarkers of the three study groups. Results The average pre-conception BMI in each group suggested a similar body size from the three study groups(19.12 ± 2.00 LC/GDM, 19.65 ± 2.32 Con/GDM, 19.53 ± 2.30 Con/Healthy; P = 0.647). Compared with the Con/GDM group, the OGTT-1 h and OGTT-2 h values in LC/GDM group were significantly higher (10.36 ± 1.28 mmol/L vs. 9.75 ± 0.98 mmol/L; 9.12 ± 0.98 mmol/L vs. 8.29 ± 1.06 mmol/L). Furthermore, the percentage of women who had more than one abnormal OGTT value (OGTT-1 h and OGTT-2 h) was 40% in the LC/GDM group, which was significantly higher than in the Con/GDM group (16.3%). Conclusions We observed a relationship between the pre-pregnancy LC diet and more detrimental OGTT values in patients with GDM. This finding warrants further studies to understand the effect of pre-pregnancy LC diet practice on maternal glucose tolerance. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-05059-2.
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Affiliation(s)
- Yanhui Hao
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China.,Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China
| | - Lei Qu
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Yuna Guo
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Liying Ma
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Muhe Guo
- Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Yiqing Zhu
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Yan Jin
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Qin Gu
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Yue Zhang
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China
| | - Wenguang Sun
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, 200030, Shanghai, China.
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35
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Xu F, Zhu Y, Lu M, Qin L, Zhao D, Ren T. Effects of Hydroxy-Alpha-Sanshool on Intestinal Metabolism in Insulin-Resistant Mice. Foods 2022; 11:foods11142040. [PMID: 35885283 PMCID: PMC9322383 DOI: 10.3390/foods11142040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
To explore the hydroxy-alpha-sanshool (HAS) effects on the intestinal metabolites of insulin-resistant mice, the blank group (BG), model group (MG), and HAS dose group (DG) were designed. The insulin resistance (IR) model was induced through streptozotocin (STZ) combined with a high-fat and high-sugar diet. Based on the availability of the model, the HAS dose was given by gavage for 28 days. The determination of cecum and key serum indexes was made, including the contents of insulin (INS), triglycerides (TG), total cholesterol (TC), glycosylated serum protein (GSP), and glycosylated hemoglobin (GHb). The changes in gut microbiota and metabolites in cecal contents were detected by 16S rRNA gene amplicon sequencing and UPLC/HRMS technology, respectively. The results that the levels of GSP, GHb, TG, and TC were significantly increased; this was not the case for INS; or for the changes in the gut microbiota and metabolites in MG. However, the intervention of HAS effectively reversed these changes, for instance, it decreased levels of GSP, GHb, TG, TC, and alterations of metabolite composition for linoleic acid and tyrosine metabolism and recovered trends of declining species diversity and richness of the gut microbiota in MG. It was indicated that HAS alleviated IR by regulating the gut microbiota and metabolites and affecting lipid and amino acid metabolism pathways.
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Affiliation(s)
- Fangyan Xu
- College of Brewing and Food Engineering, Guizhou University, Guiyang 550025, China; (F.X.); (M.L.); (L.Q.); (D.Z.)
| | - Yuping Zhu
- School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China;
| | - Mintao Lu
- College of Brewing and Food Engineering, Guizhou University, Guiyang 550025, China; (F.X.); (M.L.); (L.Q.); (D.Z.)
| | - Likang Qin
- College of Brewing and Food Engineering, Guizhou University, Guiyang 550025, China; (F.X.); (M.L.); (L.Q.); (D.Z.)
| | - Degang Zhao
- College of Brewing and Food Engineering, Guizhou University, Guiyang 550025, China; (F.X.); (M.L.); (L.Q.); (D.Z.)
- Guiyang Station for DUS Testing Center of New Plant Varieties of the Ministry of Agriculture and Rural Affairs of the People’s Republic of China in Guizhou Academy of Agricultural Sciences, Guiyang 550006, China
| | - Tingyuan Ren
- College of Brewing and Food Engineering, Guizhou University, Guiyang 550025, China; (F.X.); (M.L.); (L.Q.); (D.Z.)
- Guiyang Station for DUS Testing Center of New Plant Varieties of the Ministry of Agriculture and Rural Affairs of the People’s Republic of China in Guizhou Academy of Agricultural Sciences, Guiyang 550006, China
- Correspondence:
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Alizadeh H. Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator. Cytokine 2022; 157:155952. [PMID: 35780711 DOI: 10.1016/j.cyto.2022.155952] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 06/04/2022] [Accepted: 06/20/2022] [Indexed: 11/25/2022]
Abstract
Metrnl is a secreted protein able to activate different intracellular signaling pathways in adipocytes, macrophages, myocytes and cardiomyocytes with physiological effects of the browning of white adipose tissue (BWT), insulin sensitivity, inflammation inhibition, skeletal muscle regeneration and heart protection. Shown to be regulated by obesity, diabetes, caloric restriction, weight loss and heart diseases, Metrnl is definitely involved in metabolic turbulences, and may play roles in metabolic syndrome (MetS). However, due to the conflicting data yielded, Metrnl is still far from clinical application as a diagnostic and/or a therapeutic agent or even a therapeutic target in MetS-related diseases such as type 2 diabetes (T2D) and obesity. Nevertheless, blood Metrnl levels as well as Metrnl as a cardiokine have been reported to play cardioprotective roles against heart diseases. Considering the established metabolic and anti-inflammatory hallmarks, exercise-induced Metrnl (as a myokine) is regarded as an exercise mediator in improving obesity-induced complications such as insulin resistance, T2D and inflammation. Besides, due to its healing role in muscle damage, Metrnl is also a potential therapeutic candidate to enhance regeneration with ageing or other inflammatory myopathies like Duchenne muscular dystrophy (DMD). Therefore, there are still many exercise-related questions unanswered on Metrnl, such as Metrnl-mediated fat browning in humans, exercise effects on heart Metrnl production and secretion and the effects of other exercise-induced skeletal muscle stressors like hypoxia and oxidative in Metrnl production other than exercise-induced muscle damage.
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Affiliation(s)
- Hamid Alizadeh
- Exercise Physiology, University of Mazandaran, Babolsar, Mazandaran, Iran.
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37
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Overview of Transcriptomic Research on Type 2 Diabetes: Challenges and Perspectives. Genes (Basel) 2022; 13:genes13071176. [PMID: 35885959 PMCID: PMC9319211 DOI: 10.3390/genes13071176] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/24/2022] [Accepted: 06/28/2022] [Indexed: 02/04/2023] Open
Abstract
Type 2 diabetes (T2D) is a common chronic disease whose etiology is known to have a strong genetic component. Standard genetic approaches, although allowing for the detection of a number of gene variants associated with the disease as well as differentially expressed genes, cannot fully explain the hereditary factor in T2D. The explosive growth in the genomic sequencing technologies over the last decades provided an exceptional impetus for transcriptomic studies and new approaches to gene expression measurement, such as RNA-sequencing (RNA-seq) and single-cell technologies. The transcriptomic analysis has the potential to find new biomarkers to identify risk groups for developing T2D and its microvascular and macrovascular complications, which will significantly affect the strategies for early diagnosis, treatment, and preventing the development of complications. In this article, we focused on transcriptomic studies conducted using expression arrays, RNA-seq, and single-cell sequencing to highlight recent findings related to T2D and challenges associated with transcriptome experiments.
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The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8278744. [PMID: 35754684 PMCID: PMC9232354 DOI: 10.1155/2022/8278744] [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: 04/01/2022] [Revised: 05/10/2022] [Accepted: 05/29/2022] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mg/dL (95% CI: -36.47 to -1.47; P=0.03) for triglyceride (TG), -8.91 mg/dL (95% CI: -14.18 to -3.63, P=0.001) for total cholesterol (TC), -4.01 mg/dL (95% CI: -10.96 to 2.95, P=0.259) for low density lipoprotein cholesterol (LDL-c), 0.32 mg/dL (95% CI: -0.74 to 1.37, P=0.557) for high density lipoprotein cholesterol (HDL-c), -8.85 mg/dL (95% CI: -14.4 to -3.29, P=0.002) for fasting blood glucose (FBG), -0.54 (95% CI: -0.81 to -0.27, P ≤ 0.001) for glycated hemoglobin (HbA1c) (%) compared with controls. There was a significant heterogeneity for the influence of curcumin on TG, LDL-c, FBG and HbA1c. Subgroup analysis revealed that the heterogeneity mainly attributed to trial period, curcumin dosage and other therapy. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with T2DM. Further studies with large-scale are still needed to confirm the results.
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Hu Z, Zhou J, Han L, Li X, Li C, Wu T, Liu J, Zhao W, Kang J, Chen X. Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice. Life Sci 2022; 304:120725. [PMID: 35751919 DOI: 10.1016/j.lfs.2022.120725] [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: 05/08/2022] [Revised: 06/09/2022] [Accepted: 06/15/2022] [Indexed: 11/26/2022]
Abstract
AIMS Diabetes mellitus (DM) is a major global health threat characterized by insulin resistance. A new tactic to ameliorate insulin resistance, thereby reversing the exacerbation of DM, is urgently needed. The work is aiming to provide a new strategy for DM treatment as well as to identify new targets. MAIN METHODS C57BL/6 N mice were raised with high-fat diet (HFD) and infused with streptozotocin (STZ) to induce diabetes. The blood glucose, serum insulin, blood lipid and oxidative stress were detected. In vitro insulin resistance model experiment has been made to examine the molecular mechanisms underlying anti-diabetic effect of potential active chemicals in human hepatocellular carcinoma cells (HepG2). KEY FINDINGS Acyclovir, an antiviral nucleotide analog, alleviates insulin resistance by reducing blood lipids as well as oxidative stress and elevating insulin sensitivity on diabetic mice, which is in accord with results in the insulin resistance model of HepG2 cells. Mechanically, acyclovir stimulates pyruvate kinase M1 (PKM1) directly to activate adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Sirtuin1 (SIRT1) signaling pathway, thus improving insulin resistance. SIGNIFICANCE The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.
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Affiliation(s)
- Zhuozhou Hu
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Jing Zhou
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Liang Han
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Xiangxiang Li
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Chun Li
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Tongyu Wu
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Jingjing Liu
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Wenyang Zhao
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Jia Kang
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
| | - Xinping Chen
- Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou 730000, PR China.
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Moriyama K, Masuda Y, Suzuki N, Yamada C, Kishimoto N, Takashimizu S, Kubo A, Nishizaki Y. Estimated Elovl6 and delta-5 desaturase activities might represent potential markers for insulin resistance in Japanese adults. J Diabetes Metab Disord 2022; 21:197-207. [PMID: 35673485 PMCID: PMC9167368 DOI: 10.1007/s40200-021-00958-1] [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: 10/04/2021] [Accepted: 12/07/2021] [Indexed: 01/31/2023]
Abstract
PURPOSE Results from a recent study indicated that lower stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with metabolically unhealthy obesity. However, this has not been extensively studied in the Japanese population. METHODS We recruited 291 Japanese subjects with serum free fatty acid profiles undergoing health examinations. Whole serum desaturase activity was estimated as the product: precursor ratio -SA/PA ratio for elongation of long-chain fatty acid family member 6 (Elovl6) and AA/DGLA for delta-5 desaturase (D5D). The determinants of Elovl6 and D5D activity were investigated using multiple regression analyses. RESULTS The Elovl6 and D5D activities exhibited a negative correlation with the logmatic-transformed TG/HDL-C ratio and TyG index. Multiple regression analyses revealed that the TG/HDL-C ratio and TyG index were negatively associated with Elovl6 and D5D activities. Most atherogenic markers were worse in the low Elovl6 or D5D activity group than in the high Elovl6 or D5D activity group. When study subjects were further stratified by TG levels, most atherogenic markers were the worst in the highest TG group in either the lowest Elovl6 or lowest D5D activity groups. CONCLUSION The estimated Elovl6 and D5D activities might be useful markers of insulin resistance in Japanese subjects.
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Affiliation(s)
- Kengo Moriyama
- Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji, Tokyo 192-0032 Japan
| | - Yumi Masuda
- Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
| | - Nana Suzuki
- Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan
| | - Chizumi Yamada
- Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
- Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
| | - Noriaki Kishimoto
- Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
- Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
| | - Shinji Takashimizu
- Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan
| | - Akira Kubo
- Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
- Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
| | - Yasuhiro Nishizaki
- Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
- Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Tokyo 151-0053 Japan
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Guo Z, Pan J, Zhu H, Chen ZY. Metabolites of Gut Microbiota and Possible Implication in Development of Diabetes Mellitus. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:5945-5960. [PMID: 35549332 DOI: 10.1021/acs.jafc.1c07851] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Diabetes mellitus is characterized by having a disorder of glucose metabolism. The types of diabetes mellitus include type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and other specific types of diabetes mellitus. Many risk factors contribute to diabetes mellitus mainly including genetics, environment, obesity, and diet. In the recent years, gut microbiota has been shown to be linked to the development of diabetes. It has been reported that the gut microbiota composition of diabetic patients is different from that of healthy people. Although the mechanism behind the abnormality remains to be explored, most hypotheses focus on the inflammation response and leaky gut in relation to the changes in production of endotoxins and metabolites derived from the intestinal flora. Consequently, the above-mentioned abnormalities trigger a series of metabolic changes, gradually leading to development of hyperglycemia, insulin resistance, and diabetes. This review is (i) to summarize the differences in gut microbiota between diabetic patients and healthy people, (ii) to discuss the underlying mechanism(s) by which how lipopolysaccharide, diet, and metabolites of the gut microbiota affect diabetes, and (iii) to provide a new insight in the prevention and treatment of diabetes.
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Affiliation(s)
- Zinan Guo
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
- School of Life Sciences, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China
| | - Jingjin Pan
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
| | - Hanyue Zhu
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
| | - Zhen-Yu Chen
- School of Life Sciences, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China
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Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes. Nutrients 2022; 14:nu14091723. [PMID: 35565691 PMCID: PMC9104474 DOI: 10.3390/nu14091723] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/16/2022] [Accepted: 04/18/2022] [Indexed: 01/27/2023] Open
Abstract
Type-2 diabetes mellitus (T2DM) is often linked with hyperglycemia, disturbed lipid profiles, inflammation, and gut dysbiosis. Omega-3 fatty acid supplementation has a vital role in the management of T2DM. As a result, a better understanding of the potential role of omega-3 fatty acids in the development and progression of T2DM by influencing the intestinal microflora will help to improve the therapeutic intervention for T2DM and related complications. Focusing on the molecular mechanisms and signaling pathways induced by omega-3 fatty acids, this paper attempts to comprehensively review and discuss the putative associations between omega-3 fatty acids, gut dysbiosis, and the pathophysiology of T2DM and its related comorbidities. In addition, we contemplate the importance of gut microbiota in T2DM prevention and treatment and ponder the role of omega-3 fatty acids in T2DM by positively modulating gut microbiota, which may lead to discovery of novel targets and therapeutic strategies thereby paving way for further comprehensive, mechanistic, and clinical studies.
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Yang T, Zhao B, Pei D. Relationship between the ApoB/ApoA-I ratio trajectory and risk of type 2 diabetes in China: a retrospective cohort study. Endocrine 2022; 76:36-43. [PMID: 35032012 DOI: 10.1007/s12020-021-02961-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 12/08/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE Little research has investigated the correlation of changes in long-term apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio with risk of new-onset type 2 diabetes (T2D) among ordinary people. Therefore, the research took long-term ApoB/ApoA-I ratio trajectories as independent variables for exploring their association with the risk of newly diagnosed T2D. METHODS Altogether 5362 non-diabetic participants with a median age of 49 were enrolled in the cohort study. Their ApoB/ApoA-I ratio trajectories from 2016 to 2019 were analyzed and grouped using group-based trajectory modeling. The Kaplan-Meier approach was employed for calculating the newly diagnosed T2D-related incidence with different ApoB/ApoA-I ratio trajectories. A log-rank test was conducted for testing the presence of statistical difference in new-onset T2D incidence among the different ApoB/ApoA-I ratio trajectory groups. A multivariate Cox proportional hazards regression model was adopted for analyzing how ApoB/ApoA-I ratio trajectory changes affected new-onset T2D. RESULTS From 2016 to 2019, 199 patients developed T2D (3% in 3 years). The incidence of T2D was 2.0%, 3.28%, 5.86%, and 6.92% for low, middle, upper, and high ApoB/ApoA-I ratio trajectories, respectively. Following adjustment of underlying confounding factors, in contrast to low ApoB/ApoA-I ratio trajectory, new-onset T2D risk ratios and hazard ratio (HR) (95% confidence intervals [CI]) for the middle lower ApoB/ApoA-I ratio trajectory, and upper middle and high ApoB/ApoA-I ratio trajectories were [HR (95% CI)] 1.35(0.88-2.08), 1.98(1.27-3.09) and 2.42(1.35-4.34), respectively, indicating high and statistically significant risks of T2D. CONCLUSION Variations of the ApoB/ApoA-I ratio trajectory exerted independent effects on the 3-year incidence of T2D. Long-term monitoring on the ApoB/ApoA-I ratio locus may help improve the identification on patients with T2D.
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Affiliation(s)
- Tengfei Yang
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bo Zhao
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dongmei Pei
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China.
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Barrett JS, Whytock KL, Strauss JA, Wagenmakers AJM, Shepherd SO. High intramuscular triglyceride turnover rates and the link to insulin sensitivity: influence of obesity, type 2 diabetes and physical activity. Appl Physiol Nutr Metab 2022; 47:343-356. [PMID: 35061523 DOI: 10.1139/apnm-2021-0631] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Large intramuscular triglyceride (IMTG) stores in sedentary, obese individuals have been linked to insulin resistance, yet well-trained athletes exhibit high IMTG levels whilst maintaining insulin sensitivity. Contrary to previous assumptions, it is now known that IMTG content per se does not result in insulin resistance. Rather, insulin resistance is caused, at least in part, by the presence of high concentrations of harmful lipid metabolites, such as diacylglycerols and ceramides in muscle. Several mechanistic differences between obese sedentary individuals and their highly trained counterparts have been identified, which determine the differential capacity for IMTG synthesis and breakdown in these populations. In this review, we first describe the most up-to-date mechanisms by which a low IMTG turnover rate (both breakdown and synthesis) leads to the accumulation of lipid metabolites and results in skeletal muscle insulin resistance. We then explore current and potential exercise and nutritional strategies that target IMTG turnover in sedentary obese individuals, to improve insulin sensitivity. Overall, improving IMTG turnover should be an important component of successful interventions that aim to prevent the development of insulin resistance in the ever-expanding sedentary, overweight and obese populations. Novelty: A description of the most up-to-date mechanisms regulating turnover of the IMTG pool. An exploration of current and potential exercise/nutritional strategies to target and enhance IMTG turnover in obese individuals. Overall, highlights the importance of improving IMTG turnover to prevent the development of insulin resistance.
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Affiliation(s)
- J S Barrett
- Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool, UK
| | - K L Whytock
- Translational Research Institute, AdventHealth, Orlando, FL 32804, USA
| | - J A Strauss
- Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool, UK
| | - A J M Wagenmakers
- Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool, UK
| | - S O Shepherd
- Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool, UK
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Pereira MJ, Vranic M, Kamble PG, Jernow H, Kristófi R, Holbikova E, Skrtic S, Kullberg J, Svensson MK, Hetty S, Eriksson JW. CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage? Transl Res 2022; 242:105-121. [PMID: 34896253 DOI: 10.1016/j.trsl.2021.12.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 11/16/2021] [Accepted: 12/06/2021] [Indexed: 10/19/2022]
Abstract
CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. Functional studies included adipocyte glucose uptake and lipolysis rates. CRISPR/Cas9 CDKN2C gene knockdown was performed in human preadipocytes to assess adipogenesis. CDKN2C mRNA expression in SAT and OAT was reduced in T2D and obese subjects compared to controls. CDKN2C expression in SAT was inversely correlated with measures of hyperglycemia, insulin resistance and visceral adiposity and positively correlated with expression of genes in several metabolic pathways, including insulin signaling and fatty acid and carbohydrate metabolism. CDKN2C protein was mainly expressed in adipocytes compared to stromal vascular cells, and its gene and protein expression was up-regulated during adipocyte differentiation. Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage.
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Affiliation(s)
- Maria J Pereira
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
| | - Milica Vranic
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Prasad G Kamble
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Henning Jernow
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Robin Kristófi
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Ema Holbikova
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Stanko Skrtic
- Innovation Strategies & External Liaison, Pharmaceutical Technologies & Development, AstraZeneca, Gothenburg, Sweden; Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Joel Kullberg
- Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Maria K Svensson
- Department of Medical Sciences, Renal Medicine, Uppsala University, Uppsala, Sweden
| | - Susanne Hetty
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Jan W Eriksson
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
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Sherwood JS, Ullal J, Kutney K, Hughan KS. Cystic fibrosis related liver disease and endocrine considerations. J Clin Transl Endocrinol 2022; 27:100283. [PMID: 35024343 PMCID: PMC8724940 DOI: 10.1016/j.jcte.2021.100283] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 12/12/2022] Open
Abstract
Cystic fibrosis-liver disease (CFLD) is one of the most common non-pulmonary complications in the CF population, is associated with significant morbidity and represents the third leading cause of mortality in those with CF. CFLD encompasses a broad spectrum of hepatobiliary manifestations ranging from mild transaminitis, biliary disease, hepatic steatosis, focal biliary cirrhosis and multilobular biliary cirrhosis. The diagnosis of CFLD and prediction of disease progression remains a clinical challenge. The identification of novel CFLD biomarkers as well as the role of newer imaging techniques such as elastography to allow for early detection and intervention are active areas of research focus. Biliary cirrhosis with portal hypertension represents the most severe spectrum of CFLD, almost exclusively develops in the pediatric population, and is associated with a decline in pulmonary function, poor nutritional status, and greater risk of hospitalization. Furthermore, those with CFLD are at increased risk for vitamin deficiencies and endocrinopathies including CF-related diabetes, CF-related bone disease and hypogonadism, which can have further implications on disease outcomes and management. Effective treatment for CFLD remains limited and current interventions focus on optimization of nutritional status, identification and treatment of comorbid conditions, as well as early detection and management of CFLD specific sequelae such as portal hypertension or variceal bleeding. The extent to which highly effective modulator therapies may prevent the development or modify the progression of CFLD remains an active area of research. In this review, we discuss the challenges with defining and evaluating CFLD and the endocrine considerations and current management of CFLD.
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Key Words
- APRI, aspartate aminotransferase to platelet ratio
- BMI, body mass index
- CFBD, CF bone disease
- CFLD, Cystic fibrosis-liver disease
- CFRD, CF related diabetes
- CFTR, cystic fibrosis transmembrane conductance regulator
- Cirrhosis
- Cystic fibrosis liver disease
- Cystic fibrosis-related diabetes
- FFA, free fatty acids
- Fib-4, Fibrosis-4
- GH, growth hormone
- IGF-1, insulin-like growth factor-1
- Insulin resistance
- UDCA, ursodeoxycholic acid
- ULN, upper limit of normal
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Affiliation(s)
- Jordan S. Sherwood
- Department of Pediatrics, Diabetes Research Center, Division of Pediatric Endocrinology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, United States
| | - Jagdeesh Ullal
- Department of Medicine, UPMC Center for Diabetes and Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States
| | - Katherine Kutney
- Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Kara S. Hughan
- Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States
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Lee B, Kim SY, Cho BW, Suh S, Park KK, Choi YS. Preoperative Carbohydrate Drink Intake Increases Glycemic Variability in Patients with Type 2 Diabetes Mellitus in Total Joint Arthroplasty: A Prospective Randomized Trial. World J Surg 2022; 46:791-799. [PMID: 35006328 DOI: 10.1007/s00268-021-06437-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Preoperative carbohydrate treatment attenuates insulin resistance and improves metabolism to an anabolic state. Despite these benefits, impaired glycemic control and aspiration risk related to gastroparesis represent concerns for patients with diabetes undergoing surgery. This randomized controlled trial investigated the effects of oral carbohydrate therapy on perioperative glucose variability, metabolic responses, and gastric volume in diabetic patients undergoing elective total hip or knee arthroplasty. METHODS Fifty diabetic patients scheduled to undergo elective total knee or hip arthroplasty during August 2019-October 2020 were randomly assigned to a control or carbohydrate therapy (CHO) group. CHO group of patients received a 400-mL carbohydrate drink 2-3 h before anesthesia; control group of patients underwent overnight fasting from midnight, one night before surgery. Blood glucose levels were measured before intake of the carbohydrate drink, before spinal anesthesia, preoperatively, immediately postoperatively, and 1 h postoperatively. Insulin level and gastric volume were measured before spinal anesthesia. RESULTS The glucose variability of patients in the CHO group was significantly higher than that of those in the control group (16.5 vs. 10.1%, P = 0.008). Similarly, insulin resistance was higher in the CHO group than in the control group (8.5 vs. 2.7, P < 0.001). The gastric volume did not differ significantly between the groups (61.3 vs. 15.2 ml, P = 0.082). CONCLUSIONS Preoperative oral carbohydrate therapy increases glucose variability and insulin resistance in diabetic patients. Therefore, carbohydrate beverages should be cautiously administered to diabetic patients, considering metabolic and safety aspects. Trial registration number ClinicalTrials.gov (No. NCT04013594).
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Affiliation(s)
- Bora Lee
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - So Yeon Kim
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Byung Woo Cho
- Department of Orthopedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Sungmin Suh
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Kwan Kyu Park
- Department of Orthopedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
| | - Yong Seon Choi
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
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Lee CH, Chiang CF, Lin FH, Kuo FC, Su SC, Huang CL, Li PF, Liu JS, Lu CH, Hsieh CH, Hung YJ, Shieh YS. PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle. Front Endocrinol (Lausanne) 2022; 13:1053882. [PMID: 36619574 PMCID: PMC9816868 DOI: 10.3389/fendo.2022.1053882] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 12/09/2022] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Endoplasmic reticulum (ER) stress has emerged as a key player in insulin resistance (IR) progression in skeletal muscle. Recent reports revealed that ER stress-induced the expression of protein disulfide isomerase family a member 4 (PDIA4), which may be involved in IR-related diseases. A previous study showed that metformin modulated ER stress-induced IR. However, it remained unclear whether metformin alleviated IR by regulating PDIA4 expression in skeletal muscle. METHODS Herein, we used palmitate-induced IR in C2C12 cells and a high-fat diet-induced IR mouse model to document the relations between metformin, IR, and PDIA4. RESULTS In C2C12 cells, palmitate-induced IR increased inflammatory cytokines and PDIA4 expression. Besides, knocking down PDIA4 decreased palmitate-induced IR and inflammation in C2C12 cells. Furthermore, metformin modulated PDIA4 expression and alleviated IR both in vitro and in vivo. In addition, serum PDIA4 concentrations are associated with IR and inflammatory cytokines levels in human subjects. DISCUSSION Thus, this study is the first to demonstrate that PDIA4 participates in the metformin-induced effects on skeletal muscle IR and indicates that PDIA4 is a potential novel therapeutic target for directly alleviating IR.
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Affiliation(s)
- Chien-Hsing Lee
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan
- *Correspondence: Chien-Hsing Lee,
| | - Chi-Fu Chiang
- School of Dentistry, National Defense Medical Center, Taipei, Taiwan
| | - Fu-Huang Lin
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Feng-Chih Kuo
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sheng-Chiang Su
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chia-Luen Huang
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Peng-Fei Li
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jhih-Syuan Liu
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chieh-Hua Lu
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Hsun Hsieh
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Jen Hung
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Shing Shieh
- Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan
- School of Dentistry, National Defense Medical Center, Taipei, Taiwan
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OUP accepted manuscript. J Pharm Pharmacol 2022; 74:973-984. [DOI: 10.1093/jpp/rgac021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 03/22/2022] [Indexed: 11/13/2022]
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Martínez-Montoro JI, Damas-Fuentes M, Fernández-García JC, Tinahones FJ. Role of the Gut Microbiome in Beta Cell and Adipose Tissue Crosstalk: A Review. Front Endocrinol (Lausanne) 2022; 13:869951. [PMID: 35634505 PMCID: PMC9133559 DOI: 10.3389/fendo.2022.869951] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/08/2022] [Indexed: 12/12/2022] Open
Abstract
In the last decades, obesity has reached epidemic proportions worldwide. Obesity is a chronic disease associated with a wide range of comorbidities, including insulin resistance and type 2 diabetes mellitus (T2D), which results in significant burden of disease and major consequences on health care systems. Of note, intricate interactions, including different signaling pathways, are necessary for the establishment and progression of these two closely related conditions. Altered cell-to-cell communication among the different players implicated in this equation leads to the perpetuation of a vicious circle associated with an increased risk for the development of obesity-related complications, such as T2D, which in turn contributes to the development of cardiovascular disease. In this regard, the dialogue between the adipocyte and pancreatic beta cells has been extensively studied, although some connections are yet to be fully elucidated. In this review, we explore the potential pathological mechanisms linking adipocyte dysfunction and pancreatic beta cell impairment/insulin resistance. In addition, we evaluate the role of emerging actors, such as the gut microbiome, in this complex crosstalk.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- *Correspondence: José Ignacio Martínez-Montoro, ; Francisco J. Tinahones,
| | - Miguel Damas-Fuentes
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - José Carlos Fernández-García
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
| | - Francisco J. Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
- *Correspondence: José Ignacio Martínez-Montoro, ; Francisco J. Tinahones,
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