Effects of diet-induced obesity on protein expression in insulin signaling pathways of skeletal muscle in male Wistar rats

• Published in: International journal of general medicine Vol. 5; no. default; pp. 573 - 582
• Main Authors: Fatani, Sameer, Abubakari, Abdul-Razak, Itua, Imose, Wong, Christopher, Thomas, Cecil, Naderali, Ebrahim K
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2012; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Animals; Development and progression; Diabetes; Diet; diet-induced obesity; fenofibrate; Genetic aspects; Glucose; Insulin; Insulin resistance; insulin signaling; intramuscular lipids; Kinases; muscle; Muscles; Musculoskeletal system; Obesity; Original Research; Physiological aspects; Prognosis; Proteins; Risk factors; Rodents; Type 2 diabetes; United Kingdom; intramuscular lipids; fenofibrate; insulin signaling; diet-induced obesity; muscle
• ISSN: 1178-7074; 1178-7074
• DOI: 10.2147/IJGM.S31819

The prevalence of diet-induced obesity is increasing globally, and posing significant health problems for millions of people worldwide. Diet-induced obesity is a major contributor to the global pandemic of type 2 diabetes mellitus. The reduced ability of muscle tissue to regulate glucose homeostasis plays a major role in the development and prognosis of type 2 diabetes. In this study, an animal model of diet-induced obesity was used to elucidate changes in skeletal muscle insulin signaling in obesity-induced diabetes. Adult male Wistar rats were randomized and assigned to either a control group or to a test group. Controls were fed a standard laboratory pellet diet (chow-fed), while the test group had free access to a highly palatable diet (diet-fed). After 8 weeks, the diet-fed animals were subdivided into three subgroups and their diets were altered as follows: diet-to-chow, diet-fed with addition of fenofibrate given by oral gavage for a further 7 weeks, or diet-fed with vehicle given by oral gavage for a further 7 weeks, respectively. Untreated diet-fed animals had a significantly higher body weight and metabolic profile than the control chow-fed animals. Intramuscular triacylglyceride levels in the untreated obese animals were significantly higher than those in the control chow-fed group. Expression of protein kinase C beta, phosphatidylinositol 3, Shc, insulin receptor substrate 1, ERK1/2, and endothelial nitric oxide synthase was significantly increased by dietary obesity, while that of insulin receptor beta, insulin receptor substrate 1, and protein kinase B (Akt) were not affected by obesity. These data suggest that diet-induced obesity affects insulin signaling mechanisms, leading to insulin resistance in muscle.