Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are
strain dependent and determine oxidative stress and energy expenditure but not
insulin sensitivity.
Authors Boudina S, Sena S, Sloan C, Tebbi A, Han YH, O'Neill BT, Cooksey RC, Jones D,
Holland WL, McClain DA, Abel ED
Submitted By E. Dale Abel on 3/4/2015
Status Published
Journal Endocrinology
Year 2012
Date Published 6/1/2012
Volume : Pages 153 : 2677 - 2688
PubMed Reference 22510273
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.


Investigators with authorship
NameInstitution
E. Dale AbelUniversity of Iowa

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