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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model
Experimental Physiology, Volume 96, No. 2, Year 2011
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Description
Pro-inflammatory and stress-activated signalling 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 tumour necrosis factor-α (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 signalling 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, nuclear factor-κB, p38 MAPK and phosphoinositide 3-kinase signalling 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 were dyslipidaemic. Significant increases in the ubiquitin ligase and MuRF-1, as well as in caspase-3 and poly-ADP-ribose polymerase cleavage were observed in the muscle of obese animals compared with the control rats. We propose that dyslipidaemia may be a mechanism for the activation of inflammatory/stress-activated signalling pathways in obesity and type II diabetes, which will lead to apoptosis and atrophy in skeletal muscle. © 2010 The Authors. Journal compilation © 2011 The Physiological Society.
Authors & Co-Authors
Sishi, Balindiwe J.N.
South Africa, Stellenbosch
Stellenbosch University
Loos, Ben
South Africa, Stellenbosch
Stellenbosch University
Ellis, Beverly
South Africa, Stellenbosch
Stellenbosch University
Smith, Wayne
South Africa, Stellenbosch
Stellenbosch University
Du Toit, Eugène Francois
South Africa, Stellenbosch
Stellenbosch University
Engelbrecht, Anna Mart
South Africa, Stellenbosch
Stellenbosch University
Statistics
Citations: 128
Authors: 6
Affiliations: 1
Identifiers
Doi:
10.1113/expphysiol.2010.054189
e-ISSN:
1469445X
Research Areas
Cancer
Noncommunicable Diseases
Participants Gender
Male