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

Abstract

BackgroundThe 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.MethodsAdult 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.ResultsUntreated 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.ConclusionThese data suggest that diet-induced obesity affects insulin signaling mechanisms, leading to insulin resistance in muscle.

High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression

“…For instance consistent with our findings, reductions in expression of INSR and IRS1 during obesity [101-103] or hyperinsulinemia [96, 97] have been reported, while in contrast, increased phosphorylation of both IRS1 and IRS2 with obesity have been also observed in other cell types [45, 96, 104-107]. Additionally, other studies have observed no effect of obesity on INSR [3, 42] or IRS1 [3, 108, 109]. Taken together, these results implicate the effect of obesity on insulin signaling members to be a complex mechanism that may be species-, tissue- and/or time-specific.…”

Prenatal Testosterone Exposure Leads to Gonadal Hormone-Dependent Hyperinsulinemia and Gonadal Hormone-Independent Glucose Intolerance in Adult Male Rat Offspring1

“…The question arises as to how androgens provoke glucose intolerance and insulin resistance. The presence of reduced IRβ protein levels in the skeletal muscle, which is the major glucose utilizer and contributor of insulin resistance [ 83 ] in both intact and orchiectomized TP-exposed males, suggests that prenatal testosterone exposure induces reduced insulin signaling, which may contribute to glucose intolerance.…”

A combined continuous and interval aerobic training improves metabolic syndrome risk factors in men

“…This steady increase in the maximum leg strength signifies non-saturation index (desensitization) to the volume and intensity of the exercises prescribed in our program. Furthermore, progressive improvement in leg strength seen in our study may be at least in part due to reduction in intramuscular triacylglyceride 33 and increase in capillary density, muscle mass, citrate synthetase activity, cellular oxidative capacity, and maximal stroke volume that limits VO 2 max. 8 , 44 …”

“…Indeed, reductions observed in circulating plasma glucose and insulin as well as increase in VO 2 max in TTG provide plausible arguments for above hypotheses. Other possible explanations may include interference of high level of intramuscular triacylglycerides, 33 or alterations in insulin responsiveness of muscle fibers. 34 However, further mechanistic studies are required to elucidate the exact mechanism(s) involved in muscular weakness in T2DM.…”