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Feeding animals with diets high in saturated fat induces insulin resistance, and replacing saturated fat isocalorically with poly-unsaturated fat, especially long-chain omega-3 fatty acids, will prevent the development of insulin resistance in skeletal-muscle tissue. To investigate the mechanism, rats were fed on high-fat (20%, w/w) semipurified diets for 6 weeks. Diets containing ratios of polyunsaturated/saturated (P/S) fatty acid of 0.25 (low-P/S diet) and 1.0 (high-P/S diet) were used to study the effect of the level of saturated fat. To study the effects of omega-3 fatty acids, diets with a low-P/S ratio containing either 0 (low-omega-3 diet) or 3.3% (high-omega-3 diet) long-chain omega-3 fatty acids from fish oil were fed. Plasma membrane from skeletal muscle was purified. The content of fatty acids in sarcolemmal phospholipid was significantly related to the dietary composition. Insulin binding to intact sarcolemmal vesicles prepared from rats fed on diets high in omega-3 fatty acids increased 14-fold compared with animals fed on the low-omega-3 diet (P &amp;lt; 0.0001). Feeding rats on a diet with a high P/S ratio increased sarcolemmal insulin binding by 2.3-fold (P &amp;lt; 0.05). Increased insulin binding was due to increased receptor number at the low-affinity high-capacity binding site. Dietary effects on insulin binding were eliminated when studies were carried out on detergent-solubilized membranes, indicating the importance of the phospholipid fatty acyl composition for insulin binding. The results suggest that dietary omega-3 and polyunsaturated fatty acids increase insulin binding to sarcolemma by changing the fatty acyl composition of phospholipid surrounding the insulin receptor, and this might be the mechanism by which dietary fatty acids modify insulin action.

Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma.