Conclusions
These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity.
Methods
Twenty-nine males were overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle protein extracts, and muscle ceramide measures were obtained before and after the intervention.
Objective
Intramyocellular lipid (IMCL) is inversely related to insulin sensitivity in sedentary populations, yet no prospective studies in humans have examined IMCL accumulation with overfeeding.
Results
Eight weeks of overfeeding did not increase overall IMCL. The content of smaller lipid droplets peripherally located in the myofiber decreased, while increases in larger droplets correlated inversely with glucose disposal rate. Overfeeding resulted in inhibition of Akt activity, which correlated with the reductions in smaller, peripherally located lipid droplets and drastic increases in ceramide content. Additionally, peripherally located lipid droplets were associated with more efficient lipid oxidation. Finally, participants who maintained a greater number of smaller, peripherally located lipid droplets displayed a better resistance to weight gain with overfeeding. Conclusions: These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity.
Trial registration
ClinicalTrials.gov NCT01672632.