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