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Diabetologia
Published in: Diabetologia 11/2012

01-11-2012 | Article

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance

Authors: R. Palanivel, M. D. Fullerton, S. Galic, J. Honeyman, K. A. Hewitt, S. B. Jorgensen, G. R. Steinberg

Published in: Diabetologia | Issue 11/2012

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Abstract

Aims/hypothesis

Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known.

Methods

We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed.

Results

The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic–euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1).

Conclusions/interpretation

These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.
Appendix
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Metadata
Title
Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance
Authors
R. Palanivel
M. D. Fullerton
S. Galic
J. Honeyman
K. A. Hewitt
S. B. Jorgensen
G. R. Steinberg
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 11/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2665-3

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