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Diabetologia
Published in: Diabetologia 6/2011

01-06-2011 | Article

Amelioration of lipid-induced insulin resistance in rat skeletal muscle by overexpression of Pgc-1β involves reductions in long-chain acyl-CoA levels and oxidative stress

Authors: L. E. Wright, A. E. Brandon, A. J. Hoy, G.-B. Forsberg, C. J. Lelliott, J. Reznick, L. Löfgren, J. Oscarsson, M. Strömstedt, G. J. Cooney, N. Turner

Published in: Diabetologia | Issue 6/2011

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Abstract

Aims/Hypothesis

To determine if acute overexpression of peroxisome proliferator-activated receptor, gamma, coactivator 1 beta (Pgc-1β [also known as Ppargc1b]) in skeletal muscle improves insulin action in a rodent model of diet-induced insulin resistance.

Methods

Rats were fed either a low-fat or high-fat diet (HFD) for 4 weeks. In vivo electroporation was used to overexpress Pgc-1β in the tibialis cranialis (TC) and extensor digitorum longus (EDL) muscles. Downstream effects of Pgc-1β on markers of mitochondrial oxidative capacity, oxidative stress and muscle lipid levels were characterised. Insulin action was examined ex vivo using intact muscle strips and in vivo via a hyperinsulinaemic–euglycaemic clamp.

Results

Pgc-1β gene expression was increased >100% over basal levels. The levels of proteins involved in mitochondrial function, lipid metabolism and antioxidant defences, the activity of oxidative enzymes, and substrate oxidative capacity were all increased in muscles overexpressing Pgc-1β. In rats fed a HFD, increasing the levels of Pgc-1β partially ameliorated muscle insulin resistance, in association with decreased levels of long-chain acyl-CoAs (LCACoAs) and increased antioxidant defences.

Conclusions

Our data show that an increase in Pgc-1β expression in vivo activates a coordinated subset of genes that increase mitochondrial substrate oxidation, defend against oxidative stress and improve lipid-induced insulin resistance in skeletal muscle.
Appendix
Available only for authorised users
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Metadata
Title
Amelioration of lipid-induced insulin resistance in rat skeletal muscle by overexpression of Pgc-1β involves reductions in long-chain acyl-CoA levels and oxidative stress
Authors
L. E. Wright
A. E. Brandon
A. J. Hoy
G.-B. Forsberg
C. J. Lelliott
J. Reznick
L. Löfgren
J. Oscarsson
M. Strömstedt
G. J. Cooney
N. Turner
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2068-x

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