Fatty acids, triglycerides and syndromes of insulin resistance.

Muscle plays a major role in insulin-stimulated glucose disposal. There is now a range of evidence in humans and experimental animals demonstrating strong relationships between the fatty acid composition of structural membrane lipids and insulin action. The in vivo work is correlative but the in vitro studies suggest a causal relationship exists. Good insulin action is associated with an increased proportion of n-3 fatty acids, low saturates, a low n-6/n-3 ratio and possibly increased monounsaturates. What is reassuring is that there is a pleasing symmetry with the fatty acid pattern that might lead to decreased thrombosis. There is little argument about saturated fats with a reduction having a range of beneficial effects. However, the n-3 fatty acids might also be a key to amelioration of both insulin resistance and thrombosis. The sites of action of n-3s are multiple: decreased triglyceride and VLDL production; inhibition of thromboxane A2 production, increased thromboxane A3 and decreased platelet aggregation; reduction of triglyceride and VLDL concentration; improved blood rheology and membrane transport; action on the endothelium and proliferation of the intimal cells, and improvement of vascular tone. The data here are now strong and reasonably consistent. Similarly, after initial controversy, the evidence for n-3s playing a beneficial role in insulin action is now accumulating. The n-6 PUFAs are a bit of a worry: while arachidonic acid levels in muscle phospholipid has linked positively to insulin action in our studies, linoleic is negative. Linoleic acid, in high amounts, is known to inhibit the delta6 fatty acid desaturase enzyme and with the competition between n-6 and n-3 fatty acids for the enzymes of desaturation and elongation it does focus on a high n-6/n-3 ratio as a critical factor in both insulin resistance and atherosclerosis.