Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

Sihem Boudina; Sandra Sena; Crystal Sloan; Ali Tebbi; Yong Hwan Han; Brian T O'Neill; Robert C Cooksey; Deborah Jones; William L Holland; Donald A McClain; E. Dale Abel

doi:10.1210/en.2011-2147

Back

Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

Journal article

Open access

Peer reviewed

Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

Sihem Boudina, Sandra Sena, Crystal Sloan, Ali Tebbi, Yong Hwan Han, Brian T O'Neill, Robert C Cooksey, Deborah Jones, William L Holland, Donald A McClain, …

Endocrinology (Philadelphia), Vol.153(6), pp.2677-2688

06/01/2012

DOI: 10.1210/en.2011-2147

PMCID: PMC3359615

PMID: 22510273

Files and links (1)

url

https://doi.org/10.1210/en.2011-2147View

Published (Version of record) Open Access

Abstract

This study sought to elucidate the relationship between skeletal muscle mitochondrial dysfunction, oxidative stress, and insulin resistance in two mouse models with differential susceptibility to diet-induced obesity. We examined the time course of mitochondrial dysfunction and insulin resistance in obesity-prone C57B and obesity-resistant FVB mouse strains in response to high-fat feeding. After 5 wk, impaired insulin-mediated glucose uptake in skeletal muscle developed in both strains in the absence of any impairment in proximal insulin signaling. Impaired mitochondrial oxidative capacity preceded the development of insulin resistant glucose uptake in C57B mice in concert with increased oxidative stress in skeletal muscle. By contrast, mitochondrial uncoupling in FVB mice, which prevented oxidative stress and increased energy expenditure, did not prevent insulin resistant glucose uptake in skeletal muscle. Preventing oxidative stress in C57B mice treated systemically with an antioxidant normalized skeletal muscle mitochondrial function but failed to normalize glucose tolerance and insulin sensitivity. Furthermore, high fat-fed uncoupling protein 3 knockout mice developed increased oxidative stress that did not worsen glucose tolerance. In the evolution of diet-induced obesity and insulin resistance, initial but divergent strain-dependent mitochondrial adaptations modulate oxidative stress and energy expenditure without influencing the onset of impaired insulin-mediated glucose uptake.

Details

Title: Subtitle: Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity
Creators: Sihem Boudina - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112, Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Sandra Sena - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112, Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Crystal Sloan - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112
Ali Tebbi - Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Yong Hwan Han - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112, Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Brian T O'Neill - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112, Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Robert C Cooksey - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112
Deborah Jones - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112
William L Holland - Touchstone Diabetes Center (W.L.H.), University of Texas Southwestern Medical Center, Dallas, Texas 75390
Donald A McClain - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112
E. Dale Abel - Division of Endocrinology, Metabolism, and Diabetes (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., R.C.C., D.J., D.A.M., E.D.A.), Salt Lake City, Utah 84112, Program in Molecular Medicine (S.B., S.S., C.S., A.T., Y.H.H., B.T.O., E.D.A.), Salt Lake City, Utah 84112
Resource Type: Journal article
Publication Details: Endocrinology (Philadelphia), Vol.153(6), pp.2677-2688
DOI: 10.1210/en.2011-2147
PMID: 22510273
PMCID: PMC3359615
ISSN: 0013-7227
eISSN: 1945-7170
Language: English
Date published: 06/01/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025275302771

Metrics

23 Record Views

54 Times Cited - Web of Science