A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes
American Journal of Physiology. Endocrinology and Metabolism
A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E679-E686, 1998.-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
... % kcal fat, but fat composition differed [HF-mixed ϭ saturated, polyunsaturated (n-3 and n-6), and monounsaturated fatty acids; HF-saff ϭ 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 Ͻ 0.02). Basal uptake increased in HF-saffand HF-mixed-fed rats vs. HCHO-fed rats (P Ͻ 0.04). In adipocytes, HF-saff feeding decreased 2-deoxyglucose uptake vs. HF-mixed feeding and HCHO feeding (P Ͻ 0.05), but 2-deoxyglucose uptake in HF-mixed-fed rats did not differ from that in HCHO-fed rats (P Ͼ 0.05). Glucose tolerance was significantly reduced in HF-saff-fed rats but was unaffected by the HF-mixed diet. Therefore, in skeletal muscle of rats, 1) feeding a diet high in fat induces a reduction in insulinstimulated glucose uptake but 2) provides an increase in basal glucose uptake. In contrast, 3) in adipocytes, insulinstimulated glucose transport is reduced only when the highfat diet is high in n-6 polyunsaturated fatty acids but not when fat comes from these mixed sources. Glucose intolerance becomes evident when insulin resistance is seen in multiple tissues. high-fat feeding; fatty acids; rats The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.