The skeletal muscle Wnt pathway may modulate insulin resistance and muscle development in a diet-induced obese rat model.

The Wnt signaling pathway is involved in lipid metabolism and obesity development. Skeletal muscle, a pivotal tissue for metabolism, is regulated by the Wnt signaling. However, little is known of this pathway's involvement in insulin sensitivity and myogenesis in animals. The current study focused on the potential role of Wnt signaling in insulin sensitivity and myogenic events and its further impact on intramuscular fat accumulation. Obesity resistant (OR) and obesity prone (OP) rats were fed a high-fat (HF, 45% kcal fat) diet for 13 weeks. Body weight and circulating triglyceride (TG) were measured and gastrocnemius muscle was collected for analysis of gene expression and protein amount. OP rats had higher body weight and blood TG than OR, and our study demonstrated that the skeletal muscle of OR and OP rats had different levels of β-catenin, which also corresponded to the expression of Wnt downstream genes. The expression of insulin receptor substrate (IRS) was significantly lower in OP than OR skeletal muscle, as was the protein amount of phosphorylated Akt, myocyte enhancer factor-2 (MEF2), and GLUT4. Expression of Myogenic regulatory factor (Myf) 5 and Myf3 (MyoD) were decreased significantly in OP skeletal muscle when compared to OR. Additionally, intramuscular fat was higher in OP than in OR rats. Thus, we propose that the differential Wnt signaling in the skeletal muscle of OR and OP rats is highly likely associated with the differences in insulin sensitivity and myogenic capability in these two strains.