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

Diabetes ◽  
2021 ◽  
pp. db200763
Author(s):  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
Rebecca M Foright ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Lipoprotein Lipase ◽  
Weight Regain

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

2021 ◽  
Author(s):  
Ada Admin ◽  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Energy Expenditure ◽  
Lipoprotein Lipase ◽  
Weight Regain ◽  
Energy Homeostasis ◽  
Fat Metabolism ◽  
Fat Oxidation ◽  
Oxidative Capacity ◽  
Expression Of Genes

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.

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

2021 ◽  
Author(s):  
Ada Admin ◽  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Energy Expenditure ◽  
Lipoprotein Lipase ◽  
Weight Regain ◽  
Energy Homeostasis ◽  
Fat Metabolism ◽  
Fat Oxidation ◽  
Oxidative Capacity ◽  
Expression Of Genes

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.

scholarly journals 2536

2017 ◽  
Vol 1 (S1) ◽  
pp. 11-11
Author(s):  
David M. Presby ◽  
Rebecca M. Foright ◽  
Julie A. Houck ◽  
Ginger C. Johnson ◽  
L. Allyson Checkley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Total Energy ◽  
Weight Regain ◽  
Resting Metabolic Rate ◽  
Weight Loss Maintenance ◽  
Oxidative Capacity ◽  
Total Energy Expenditure

OBJECTIVES/SPECIFIC AIMS: Obesity is a rapidly growing epidemic and long-term interventions aimed to reduce body weight are largely unsuccessful due to an increased drive to eat and a reduced metabolic rate established during weight loss. Previously, our lab demonstrated that exercise has beneficial effects on weight loss maintenance by increasing total energy expenditure above and beyond the cost of an exercise bout and reducing the drive to eat when allowed to eat ad libitum (relapse). We hypothesized that exercise’s ability to counter these obesogenic-impetuses are mediated via improvements in skeletal muscle oxidative capacity, and tested this using a mouse model with augmented oxidative capacity in skeletal muscle. METHODS/STUDY POPULATION: We recapitulated the exercise-induced improvements in oxidative capacity using FVB mice that overexpress lipoprotein lipase in skeletal muscle (mLPL). mLPL and wild type (WT) mice were put through a weight-loss-weight-regain paradigm consisting of a high fat diet challenge for 13 weeks, with a subsequent 1-week calorie-restricted medium fat diet to induce a ~15% weight loss. This newly established weight was maintained for 2 weeks and followed with a 24-hour relapse. Metabolic phenotype was characterized by indirect calorimetry during each phase. At the conclusion of the relapse day, mice were sacrificed and tissues were harvested for molecular analysis. RESULTS/ANTICIPATED RESULTS: During weight loss maintenance, mLPL mice had a higher metabolic rate (p=0.0256) that was predominantly evident in the dark cycle (p=0.0015). Furthermore, this increased metabolic rate was not due to differences in activity (p=0.2877) or resting metabolic rate (p=0.4881). During relapse, mLPL mice ingested less calories and were protected from rapid weight regain (p=0.0235), despite WT mice exhibiting higher metabolic rates during the light cycle (p=0.0421). DISCUSSION/SIGNIFICANCE OF IMPACT: These results highlight the importance of muscular oxidative capacity in preventing a depression in total energy expenditure during weight loss maintenance, and in curbing overfeeding and weight regain during a relapse. Moreover, our data suggest that the thermic effect of food is responsible for the differences in metabolic rate, because no differences were found in activity or resting metabolic rate. Additional studies are warranted to determine the molecular mechanisms driving the ability of oxidative capacity to assist with weight loss maintenance.

Whole-body insulin resistance and energy expenditure indices, serum lipids, and skeletal muscle metabolome in a state of lipoprotein lipase overexpression

Metabolomics ◽  
2021 ◽  
Vol 17 (3) ◽  
Author(s):  
Yuichiro Nishida ◽  
Kazutoshi Nishijima ◽  
Yosuke Yamada ◽  
Hiroaki Tanaka ◽  
Akiko Matsumoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Lipoprotein Lipase ◽  
Serum Lipids ◽  
Whole Body

Combination of Canagliflozin and Exercise Training Leads to Lipid-Dependent Energy Expenditure in Skeletal Muscle in Obese Diabetic Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 742-P
Author(s):  
KENICHI TANAKA ◽  
HIROKAZU TAKAHASHI ◽  
KAZUYO SASAKI ◽  
KANAKO INOUE ◽  
YAYOI MATSUDA ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Exercise Training ◽  
Diabetic Mice

scholarly journals β-Adrenergically Stimulated Fat Oxidation Is Diminished in Middle-Aged Compared to Young Subjects*

1999 ◽  
Vol 84 (10) ◽  
pp. 3764-3769
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
W. H. M. Saris
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Total Energy ◽  
Fat Oxidation ◽  
Substrate Utilization ◽  
Total Energy Expenditure ◽  
Adrenergic Stimulation ◽  
Middle Aged ◽  
Older Subjects ◽  
Young Subjects

Abstract The effect of aging on β-adrenergically mediated substrate utilization was investigated in nine young (25.2 ± 1.7 yr old) and eight older males (52.9 ± 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselectiveβ -agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass·min). During β-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass·min, 31% vs. 21% of total energy expenditure; P < 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P < 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from −175 ± 32 to −366 ± 66 nmol/100 mL forearm tissue·min), whereas there was no change in young subjects (from− 32 ± 21 to 23 ± 57 nmol/100 mL forearm tissue·min; interaction group × ISO, P < 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group × ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during β-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.

scholarly journals Female rats selectively bred for high intrinsic aerobic fitness are protected from ovariectomy-associated metabolic dysfunction

2015 ◽  
Vol 308 (6) ◽  
pp. R530-R542 ◽  
Author(s):  
Victoria J. Vieira-Potter ◽  
Jaume Padilla ◽  
Young-Min Park ◽  
Rebecca J. Welly ◽  
Rebecca J. Scroggins ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Aerobic Fitness ◽  
Resting Energy Expenditure ◽  
Female Rats ◽  
Metabolic Dysfunction ◽  
Spontaneous Physical Activity ◽  
Resting Energy

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals ( r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure.

scholarly journals Energy Restriction Results in a Mass-Adjusted Decrease in Energy Expenditure in Cats That Is Maintained after Weight Regain

2008 ◽  
Vol 138 (5) ◽  
pp. 856-860 ◽  
Author(s):  
Cecilia Villaverde ◽  
Jon J. Ramsey ◽  
Alice S. Green ◽  
Danny K. Asami ◽  
Seung Yoo ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Weight Regain ◽  
Energy Restriction
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