American Diabetes Association
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Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

posted on 2021-02-03, 19:16 authored by Ada AdminAda Admin, David M Presby, Michael C Rudolph, Vanessa D Sherk, Matthew R Jackman, Rebecca M Foright, Kenneth L Jones, Julie A Houck, Ginger C Johnson, Janine A Higgins, P. Darrell Neufer, Robert H Eckel, Paul S MacLean
Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism genes were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.


This work was supported by the National Institutes of Health National Institute on Aging Grant U54 AG062319 and National Institute of Child Health and Human Development Grant P50 HD073063 (to P.S.M.); NIH Training Grant No. T32 DK007260 (to DMP); National Center for Advancing Translational Sciences fellowships TR001081 TL1 (to D.M.P.) and KL2 CDA (to V.D.S.); and NIDDK Grant K01 DK109079 (to M.C.R.). We appreciate the support from the Colorado Nutrition Obesity Research Center [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) P30 DK48520].