Distinct lipid droplet characteristics and distribution unmask the apparent contradiction of the athlete's paradox

• Published in: Molecular metabolism (Germany) Vol. 17; pp. 71 - 81
• Main Authors: Daemen, Sabine, Gemmink, Anne, Brouwers, Bram, Meex, Ruth C.R., Huntjens, Peter R., Schaart, Gert, Moonen-Kornips, Esther, Jörgensen, Johanna, Hoeks, Joris, Schrauwen, Patrick, Hesselink, Matthijs K.C.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.11.2018; Elsevier
• Subjects: Adult; Athlete's paradox; Athletes; Biopsy, Needle - methods; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - metabolism; Exercise - physiology; Female; GTP-Binding Proteins; Humans; Insulin Resistance - physiology; Insulin sensitivity; Intramyocellular lipid; Lipid droplets; Lipid Droplets - metabolism; Lipid Droplets - physiology; Lipid Metabolism - physiology; Male; Middle Aged; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - physiology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Netherlands; Obesity - metabolism; Original; Overweight - metabolism; Physical Endurance - physiology; Netherlands; Athlete's paradox; Intramyocellular lipid; Insulin sensitivity; Lipid droplets
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2018.08.004

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. 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). 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. 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. •Distinct lipid droplet morphology and distribution underlies the athletes' paradox.•Muscle lipid storage occurs in a fiber type specific manner.•Exercise training shifts LD morphology towards an athletes' phenotype.