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

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posted on 2024-05-03, 19:38 authored by Karen C. Shen, Kelsey H. Collins, Jeremie L.A. Ferey, Alan Fappi, Jeremy J. McCormick, Bettina Mittendorfer, Farshid Guilak, Gretchen A. Meyer

Observational studies show 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 metabolically normal (defined as normal fasting plasma glucose and glucose tolerance) and metabolically abnormal (defined as pre-diabetes and type 2 diabetes) people with 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 between metabolically abnormal and normal mice and among metabolically normal and metabolically abnormal people. 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 groups and the control group 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.

Funding

This study was supported by NIH Grants AR075773, AG15768, AG46927, AR072999, AR073752, P30 AR074992 (Musculoskeletal Research Center) and P30 DK056341 (Nutrition Obesity Research Center) and a grant from the Longer Life Foundation (2019-011).

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