“It Takes Two To Tango”, Exercise Modifies Skeletal Muscle Mitochondria And Lipid Droplets Closeness

Abstract

PURPOSE: Intramyocellular lipids (IMCL), stored in lipid droplets (LD), are known to be a hallmark of skeletal muscle insulin resistance. Chronic exercise (training) increases IMCL while also increasing insulin sensitivity (IS), a paradigm known as the athlete’s paradox. Mitochondria (M), the powerhouse of the cells, are responsible to transform LD content into energy. The closeness of these 2 organelles in the different subcellular compartments (intramyofribrillar (IMF) and subsarcolemmal (SSL)) and how they change with training are not yet known. The purpose of this study was to examine exercise induced changes in LD and M closeness in insulin resistant non-diabetic subjects. METHODS: In a nested case-control study, 12 cases (6F/6M) underwent a 4-months supervised endurance exercise intervention. 12 insulin sensitive subjects matched by age and gender served as controls (C). LD, M and the surface in contact with each other, were assessed in muscle biopsies with electron microscopy. IS was measured by hyperinsulinemic euglycemic clamp. VO2peak was measured by GXT and body composition by DEXA. RESULTS: Although training improved IS by 45±8% (P<0.05), increased VO2peak by 13.2±4.4% (P<0.05), reduced body fat by 3.9±1.2% (P<0.05), cases remained significantly different from C. M increased in IMF and SSL (54.7±15.1% and 78.2±20.5% respectively, P<0.05). LD increased in IMF (51.8±18.1%) and decreased in (SSL 20.7±8.3%, both P<0.05). Contact between M and LD increased significantly only in IMF (65.1±26.3%, P<0.05). While SSL LD were negatively correlated with IS at baseline, changes in overall LD with intervention were related with improvements in IS. SSL LD correlated with body adiposity, but not IMF LD. CONCLUSIONS: With endurance training, the closeness of M and LD increased only in the contractile region, i.e. the IMF compartment. At the same time, the amount of M and LD increased in this compartment. This observation confirms what is observed in healthy and athletic individuals, which suggests that IMCL are used for fuel. At the contrary, LD decreased in the SSL region while M increased in this compartment. Our observations are of interest, as IMCL are known to be involved in the mechanisms leading to insulin resistance in sedentary muscle, possibly explaining the observation in the SSL region.