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

Author:

Presby David M.1,Rudolph Michael C.2ORCID,Sherk Vanessa D.3,Jackman Matthew R.1,Foright Rebecca M.4,Jones Kenneth L.5,Houck Julie A.3,Johnson Ginger C.3,Higgins Janine A.5,Neufer P. Darrell6,Eckel Robert H.3,MacLean Paul S.3ORCID

Affiliation:

1. Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA

2. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

3. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO

4. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS

5. Department of Pediatrics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO

6. East Carolina Diabetes and Obesity Institute and the Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC

Abstract

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 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.

Funder

National Institute on Aging

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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