Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model

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Title Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model
Author Sishi, Balindiwe; Loos, Benjamin; Ellis, Beverley; Smith, Wayne; Du Toit, Eugene; Engelbrecht, Anna-Mart
Journal Name Experimental Physiology
Year Published 2011
Place of publication United Kingdom
Publisher Wiley-Blackwell Publishing Ltd
Abstract Pro-inflammatory and stress activated signaling pathways are important role players in the pathogenesis of obesity and insulin resistance. Obesity and type II diabetes are associated with chronic, low-grade inflammation and elevated TNF-α levels. There is increasing evidence that TNF-α may play a critical role in skeletal muscle atrophy. However, the effects of obesity-induced insulin resistance on these signaling pathways are poorly understood in skeletal muscle. Therefore, the present study addressed the effects of obesity-induced insulin resistance on the activity of the ubiquitin ligases, NF-κB-, p38 MAPK- and PI3-kinase signaling pathways in the gastrocnemius muscle and compared these with muscle of standard chow-fed control rats. Male Wistar rats were randomly allocated to a control diet group (standard commercial chow - 60% carbohydrates, 30% protein and 10% fat) or a cafeteria diet group (65% carbohydrates, 19% protein and 16% fat) for 16 weeks. Blood analysis was conducted to determine the impact of the model of obesity on circulating insulin, glucose, free fatty acids, TNF-α and angiotensin II concentrations. The experimental animals were 18% heavier and had 68% greater visceral fat mass than their control counterparts and was also dyslipidaemic. Significant increases in the ubiquitin ligase, MURF-1, as well as in caspase-3- and PARP cleavage were observed in the muscle of obese animals compared to the controls. We propose that dyslipidaemia may be a mechanism for the activation of inflammatory/stress activated signaling pathways in obesity and type II diabetes which will lead to apoptosis and atrophy in skeletal muscle.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1113/expphysiol.2010.054189
Copyright Statement Copyright 2010 The Physiological Society. This is the author-manuscript version of the paper. Reproduced in accordance with the copyright policy of the publisher. The definitive version is available at http://onlinelibrary.wiley.com/
Volume 96
Page from 179
Page to 193
ISSN 0958-0670
Date Accessioned 2011-04-27
Date Available 2013-05-29T09:36:21Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject Cardiovascular Medicine and Haematology; Medical Physiology; Physiology
URI http://hdl.handle.net/10072/38575
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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