Excess Intramyocellular Lipid Does Not Affect Muscle Fiber Biophysical Properties in Mice or People with Metabolically Abnormal Obesity

Observational studies have shown correlations between intramyocellular lipid (IMCL) content and muscle strength and contractile function in people with metabolically abnormal obesity. However, a clear physiologic mechanism for this association is lacking, and causation is debated. We combined immunofluorescent confocal imaging with force measurements on permeabilized muscle fibers from metabolically normal and metabolically abnormal mice and people with metabolically normal (defined as normal fasting plasma glucose and glucose tolerance) and metabolically abnormal (defined as prediabetes and type 2 diabetes) overweight/obesity to evaluate relationships among myocellular lipid droplet characteristics (droplet size and density) and biophysical (active contractile and passive viscoelastic) properties. The fiber type specificity of lipid droplet parameters varied by metabolic status and by species. It was different between mice and people across the board and different between people of different metabolic status. However, despite considerable quantities of IMCL in the metabolically abnormal groups, there were no significant differences in peak active tension or passive viscoelasticity between the metabolically abnormal and control groups in mice or people. Additionally, there were no significant relationships among IMCL parameters and biophysical variables. Thus, we conclude that IMCL accumulation per se does not impact muscle fiber biophysical properties or physically impede contraction. Article Highlights