High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass

It has been variously hypothesized that the insulin resistance induced in r odents by a high-fat diet is due to increased visceral fat accumulation, to an increase in muscle triglyceride (TG) content, or to an effect of diet c omposition. In this study we used a number of interventions: fish oil, lept in, caloric restriction, and shorter duration of fat feeding, to try to dis associate an increase in visceral fat from muscle insulin resistance. Subst ituting fish oil (18% of calories) for corn oil in the high-fat diet partia lly protected against both the increase in visceral fat and muscle insulin resistance without affecting muscle TG content. Injections of leptin during the last 4 days of a 4-wk period on the high-fat diet partially reversed t he increase in visceral fat and the muscle insulin resistance, while comple tely normalizing muscle TG. Restricting intake of the high-fat diet to 75% of ad libitum completely prevented the increase in visceral fat and muscle insulin resistance. Maximally insulin-stimulated glucose transport was nega tively correlated with visceral fat mass (P < 0.001) in both the soleus and epitrochlearis muscles and with muscle TG concentration in the soleus (P < 0.05) but not in the epitrochlearis. Thus we were unable to dissociate the increase in visceral fat from muscle insulin resistance using a variety of approaches. These results support the hypothesis that an increase in visce ral fat is associated with development of muscle insulin resistance.