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

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.

SUBMITTER: Presby DM

PROVIDER: S-EPMC7980196 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Presby David M DM Rudolph Michael C MC Rudolph Michael C MC Sherk Vanessa D VD Jackman Matthew R MR Foright Rebecca M RM Jones Kenneth L KL Houck Julie A JA Johnson Ginger C GC Higgins Janine A JA Neufer P Darrell PD Eckel Robert H RH MacLean Paul S PS

Diabetes 20210203 4

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 ...[more]

PMID: 33536195

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Project description:BACKGROUND:There are significant variations in gestational weight gain, with many women gaining in excess of the Institute of Medicine guidelines. Unfortunately, efforts to improve appropriate gestational weight gain have had only limited success. To date, interventions have focused primarily on decreasing energy intake and/or increasing physical activity. Maternal resting energy expenditure, which comprises ?60% of total energy expenditure compared with the ?20% that comes from physical activity, may be an important consideration in understanding variations in gestational weight gain. OBJECTIVE:Our objective was to quantify the changes in resting energy expenditure during pregnancy and their relationship to gestational weight gain and body composition changes among healthy women. We hypothesized that greater gestational weight gain, and fat mass accrual in particular, are inversely related to variations in resting energy expenditure. STUDY DESIGN:We conducted a secondary analysis of a prospective cohort studied before conception and late pregnancy (34-36 weeks). Body composition (estimated using hydrodensitometry) and resting energy expenditure (estimated using indirect calorimetry) were measured. The relationship between the changes in resting energy expenditure and gestational weight gain and the change in fat mass and fat-free mass were quantified. Resting energy expenditure was expressed as kilocalories per kilogram of fat-free mass per day (kilocalories per kilogram of fat-free mass-1/day-1) and kilocalories per day. Correlations are reported as r. RESULTS:Among 51 women, preconception body mass index was 23.0 (4.7) kg/m2; gestational weight gain was 12.8 (4.7) kg. Preconception and late pregnancy resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.37, P = .008; r = 0.51, P = .001). Late-pregnancy resting energy expenditure (kilocalories per kilogram of fat-free mass-1/day-1) was inversely associated with the change in fat mass (r = -0.34, P = .02) and gestational weight gain (r = -0.29, P = .04). From before pregnancy through late gestation, the increase in resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.44, P = .002) and negatively with the change in fat mass (r = -0.27, P = .06). CONCLUSION:The change in resting energy expenditure from before conception through late gestation correlated positively with changes in fat-free mass but negatively with fat mass accrual. Women with smaller increases in resting energy expenditure across pregnancy had greater gestational weight gain, specifically more adipose tissue. These data suggest that resting energy expenditure is an important factor in gestational weight gain, particularly excess fat mass accrual. Future lifestyle intervention studies need to consider clinically feasible means of estimating resting energy expenditure and, in response, tailor nutrient intake and composition recommendations. Implementing and testing such interventions would be a novel approach to improve compliance with gestational weight gain guidelines.

Dataset Information

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

Publications

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

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