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. 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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http://dx.doi.org/10.1139/apnm-2021-0631 | DOI Listing |
PLoS Biol
January 2025
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood.
View Article and Find Full Text PDFPLoS One
January 2025
Specialist in Family and Community Medicine, Milladoiro Health Centre, Health Area of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Purpose: To determine the relationship between self-reported physical activity and the components of premorbid metabolic syndrome in patients treated in primary care according to sex.
Methods: Cross-sectional descriptive study conducted on a sample of 2,359 patients without cardiovascular disease or diabetes, included in the cohort of the IBERICAN study. Using ANOVA models and adjusting for age, economic status, employment situation, level of education, adherence to a Mediterranean diet, tobacco use and alcohol consumption, we estimated the association of the variables blood pressure, triglycerides, HDL cholesterol, blood glucose and waist circumference with the self-reported level of physical activity (sedentary, moderate, high, very high).
Diabetes
January 2025
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
The homeobox (HOX) family has shown potential in adipose development and function, yet the specific HOX proteins fueling adipose thermogenesis remain elusive. In this study, we uncovered the novel function of HOXC4 in stimulating adipose thermogenesis. Our bioinformatic analysis indicated an enrichment of Hoxc4 co-expressed genes in metabolic pathways and linked HOXC4 polymorphisms to metabolic parameters, suggesting its involvement in metabolic regulation.
View Article and Find Full Text PDFDiabetes
January 2025
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.
View Article and Find Full Text PDFFASEB J
January 2025
Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, China.
Gestational Diabetes Mellitus (GDM) is the most frequent complication during pregnancy. Pharmacological interventions, such as peptide drugs that focused on improving the insulin sensitivity might be promising in the prevention and treatment of GDM. In this study, we aimed to investigate the role and mechanism of a novel peptide, named AGDMP1 (Anti-GDM peptide 1), which we previously identified lower in the serum of GDM patients using mass spectrometry, on the adipose insulin resistance in GDM.
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