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 from that in HCHO-fed rats (P > 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 insulin-stimulated glucose uptake but 2) provides an increase in basal glucose uptake. In contrast, 3) in adipocytes, insulin-stimulated glucose transport is reduced only when the high-fat 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.
Wilkes
J J
JJ
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Bonen
A
A
Bell
R C
RC
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D002149:Energy Intake; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000494:pharmacology*
D001786:Blood Glucose; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D012450:Safflower Oil