Document Detail

Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model.
MedLine Citation:
PMID:  20952489     Owner:  NLM     Status:  In-Data-Review    
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-B, 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.
Balindiwe Sishi; Benjamin Loos; Beverly Ellis; Wayne Smith; Eugene F du Toit; Anna-Mart Engelbrecht
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Publication Detail:
Type:  Journal Article     Date:  2010-10-15
Journal Detail:
Title:  Experimental physiology     Volume:  96     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  179-93     Citation Subset:  IM    
Department of Physiological Sciences, Private Bag X1, Matieland, Stellenbosch 7600, South Africa.
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