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

Sameer Fatani,¹ Abdul-Razak Abubakari,² Imose Itua,² Christopher Wong,³ Cecil Thomas,³ Ebrahim K Naderali<sup>2

1</sup>Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, ²Department of Health Sciences, Liverpool Hope University, Hope Park, ³Aintree University Hospital NHS Foundation Trust, Liverpool, UK

Background: 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.
Methods: 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.
Results: 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.
Conclusion: These data suggest that diet-induced obesity affects insulin signaling mechanisms, leading to insulin resistance in muscle.

Keywords: diet-induced obesity, intramuscular lipids, insulin signaling, muscle, fenofibrate