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
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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
Volume 96
Page from 179
Page to 193
ISSN 0958-0670
Date Accessioned 2011-04-27
Language en_US
Research Centre Menzies Health Institute Qld
Faculty Griffith Health Faculty
Subject Cardiovascular Medicine and Haematology; Medical Physiology; Physiology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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