A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes.

We hypothesized that variation in dietary fatty acid composition in rats fed a high-fat diet had tissue-specific effects on glucose uptake sufficient to maintain normal glucose tolerance. Rats were fed one of three diets for 3 wk. The isocaloric high-fat-mixed oil (HF-mixed) diet and the high-fat-safflower oil (HF-saff) diet both provided 60% kcal fat, but fat composition differed [HF-mixed = saturated, polyunsaturated (n-3 and n-6), and monounsaturated fatty acids; HF-saff = polyunsaturated fatty acids (mainly n-6)]. The control diet was high carbohydrate (HCHO, 10% kcal fat). Insulin-stimulated 3-O-methylglucose uptake into perfused hindlimb muscles was reduced in rats fed HF-saff and HF-mixed diets compared with those fed HCHO diet (P< 0.02). Basal uptake increased in HF-saff- and HF-mixed-fed rats vs. HCHO-fed rats (P < 0.04). In adipocytes, HF-saff feeding decreased 2-deoxyglucose uptake vs. HF-mixed feeding and HCHO feeding (P< 0.05), but 2-deoxyglucose uptake in HF-mixed-fed rats did not differ fro...