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 ra ts fed a high-fat diet had tissue-specific effects on glucose uptake s ufficient to maintain normal glucose tolerance. Rats were fed one of t hree 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, polyunsaturat ed (n-3 and n-6), end monounsaturated fatty acids; HF-saff = polyunsat urated fatty acids (mainly n-6)]. The control diet was high carbohydra te (HCHO, 10% kcal fat). Insulin-stimulated 3-O-methyl-glucose 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 v s. HF-mixed feeding and HCHO feeding (P < 0.05), but 2-deoxyglucose up take in HF-mixed-fed rats did not differ from that in HCHO-fed rats (P > 0.05). Glucose tolerance was significantly reduced in HF-saff-fed r ats but was unaffected by the HF-mixed diet. Therefore, in skeletal mu scle of rats, 1)feeding a diet high in fat induces a reduction in insu lin-stimulated glucose uptake but 2) provides an increase in basal glu cose uptake. In contrast, 3) in adipocytes, insulin-stimulated glucose transport is reduced only when the high-fat diet is high in n-6 polyu nsaturated fatty acids but not when fat comes from these mixed sources . Glucose intolerance becomes evident when insulin resistance is seen in multiple tissues.