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

Mol Metab. 2018 Nov:17:71-81. doi: 10.1016/j.molmet.2018.08.004. Epub 2018 Aug 18.

Abstract

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.

Keywords: Athlete's paradox; Insulin sensitivity; Intramyocellular lipid; Lipid droplets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Athletes
  • Biopsy, Needle / methods
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / metabolism
  • Exercise / physiology*
  • Female
  • GTP-Binding Proteins
  • Humans
  • Insulin Resistance / physiology
  • 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
  • Overweight / metabolism
  • Physical Endurance / physiology

Substances

  • GTP-Binding Proteins