Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice
Abstract
To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.
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Overexpression of uncoupling protein 1 in white adipose tissue or skeletal muscle can prevent diet-induced obesity in mice.
“overexpression of uncoupling protein 1 (UCP1), which increases substrate utilization and electron transport chain turnover, in white adipose tissue [50] or skeletal muscle [51] can prevent diet-induced obesity in mice”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [51]
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- Authors
- Li, B., Nolte, L. A., Ju, J.-S., Ho Han, D., Coleman, T., Holloszy, J. O., & Semenkovich, C. F.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Semenkovich, Clay F.
- Venue
- Nature Medicine
- Published
- 2000-10
- Volume
- 6
- Issue
- 10
- Pages
- 1115-1120
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2076944010
- Cited by
- 291
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 12 · 2018: 10 · 2017: 8 · 2016: 10 · 2015: 15 · 2014: 10 · 2013: 9 · 2012: 16
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk053198-04)
- National Institute on Aging (AG00425)
- National Heart, Lung, and Blood Institute (HL58427, R01HL058427)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-53198)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial uncoupling, skeletal muscle, diet-induced obesity, insulin resistance, type 2 diabetes, high-fat diet, skeletal muscle oxygen consumption, glucose tolerance, glucose transport, muscle triglycerides, metabolic rate, exercise metabolism
- MeSH terms
- Uncoupling Protein 1, Animals, Body Weight, Carrier Proteins, Diet, Female, Glucose, Insulin Resistance, Ion Channels, Male, Membrane Proteins, Mice, Transgenic, Obesity, Uncoupling Agents, Muscle, Skeletal, Cell Respiration, Mitochondrial Proteins, Mice
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