期刊
MOLECULAR METABOLISM
卷 17, 期 -, 页码 71-81出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2018.08.004
关键词
Insulin sensitivity; Athlete's paradox; Intramyocellular lipid; Lipid droplets
资金
- Dutch Diabetes Research Foundation [DF 2014.00.1756]
- Netherlands Organization for Scientific Research [022.003.011]
- NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands
- Netherlands Cardiovascular Research Initiative
- Dutch Heart Foundation [CVON2014-02 ENERGISE]
- NUTRIM-School of Nutrition and Translational Research in Metabolism - NWO Graduate Program
Objective: Intramyocellular lipid (IMCL) storage negatively associates with insulin resistance, albeit not in endurance-trained athletes. We investigated the putative contribution of lipid droplet (LD) morphology and subcellular localization to the so-called athlete's paradox. Methods: We performed quantitative immunofluorescent confocal imaging of muscle biopsy sections from endurance Trained, Lean sedentary, Obese, and Type 2 diabetes (T2DM) participants (n = 8/group). T2DM patients and Trained individuals were matched for IMCL content. Furthermore we performed this analysis in biopsies of T2DM patients before and after a 12-week exercise program (n = 8). Results: We found marked differences in lipid storage morphology between trained subjects and T2DM: the latter group mainly store lipid in larger LDs in the subsarcolemmal (SS) region of type II fibers, whereas Trained store lipid in a higher number of LDs in the intramyofibrillar (IMF) region of type I fibers. In addition, a twelve-week combined endurance and strength exercise program resulted in a LD phenotype shift in T2DM patients partly towards an 'athlete-like' phenotype, accompanied by improved insulin sensitivity. Proteins involved in LD turnover were also more abundant in Trained than in T2DM and partly changed in an 'athlete-like' fashion in T2DM patients upon exercise training. Conclusions: Our findings provide a physiological explanation for the athlete's paradox and reveal LD morphology and distribution as a major determinant of skeletal muscle insulin sensitivity. (C) 2018 The Authors. Published by Elsevier GmbH.
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