SKELETAL-MUSCLE GLUCOSE-METABOLISM IN OBESITY-PRONE AND OBESITY-RESISTANT RATS

Ad libitum access to a high-fat (HF) diet produces a wide range of wei ght gain in rats. Rats most susceptible to weight gain on such a diet (obesity prone; OP) are more insulin resistant after 4-5 wk of diet ex posure than are those most resistant (obesity resistant; OR) to weight gain. To investigate whether skeletal muscle glucose metabolism contr ibutes to insulin resistance in this model, insulin-stimulated glucose metabolism was assessed in the perfused hindquarter of rats exposed t o either a low-fat (LF, n = 6) or HF diet for 5 wk. Delineation of OP (n = 6) and OR (n = 6) rats was based on body weight gain. OP rats gai ned 60% more body weight while eating only 10% more energy than OR rat s. Single-pass perfusions were carried out for 2 h in the presence of glucose, insulin, and [U-C-14]glucose. Insulin-stimulated glucose upta ke (mumol . 100 g-1 . min-1) was 14.2 +/- 0.9 in LF, 11.1 +/- 0.8 in O R, and 6.2 +/- 0.6 in OP. Glucose oxidation (mumol . 100 g-1 . min-1) was 1.7 +/- 0.3 and 1.2 +/- 0.3 in LF and OR, respectively, but was 0. 2 +/- 0.1 in OP. Net glycogen synthesis was significantly reduced in O P compared with OR and LF despite similar glycogen synthase I activity . Muscle triglyceride concentration was not significantly different in OR and OP rats. These results demonstrate significant defects in skel etal muscle glucose uptake and disposal in rats most susceptible to HF diet-induced obesity. Clearly, the heterogeneous response to a HF die t involves not only body weight gain but also skeletal muscle fuel met abolism.