DIETARY OMEGA-3 AND POLYUNSATURATED FATTY-ACIDS MODIFY FATTY ACYL COMPOSITION AND INSULIN BINDING IN SKELETAL-MUSCLE SARCOLEMMA

Feeding animals with diets high in saturated fat induces insulin resis tance, and replacing saturated fat isocalorically with polyunsaturated fat, especially long-chain omega-3 fatty acids, will prevent the deve lopment of insulin resistance in skeletal-muscle tissue. To investigat e the mechanism, rats were fed on high-fat (20%, w/w) semipurified die ts 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 us ed to study the effect of the level of saturated fat. To study the eff ects of omega-3 fatty acids, diets with a low-P/S ratio containing eit her 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 mu scle was purified. The content of fatty acids in sarcolemmal phospholi pid was significantly related to the dietary composition. Insulin bind ing to intact sarcolemmal vesicles prepared from rats fed on diets hig h in omega-3 fatty acids increased 14-fold compared with animals fed o n the low-omega-3 diet (P < 0.0001). Feeding rats on a diet with a hig h P/S ratio increased sarcolemmal insulin binding by 2.3-fold (P < 0.0 5). Increased insulin binding was due to increased receptor number at the low-affinity high-capacity binding site. Dietary effects on insuli n binding were eliminated when studies were carried out on detergent-s olubilized membranes, indicating the importance of the phospholipid fa tty acyl composition for insulin binding. The results suggest that die tary omega-3 and polyunsaturated fatty acids increase insulin binding to sarcolemma by changing the fatty acyl composition of phospholipid s urrounding the insulin receptor, and this might be the mechanism by wh ich dietary fatty acids modify insulin action.