Long-chain fatty acid metabolism in fasting and diabetes: relation between altered desaturase activity and fatty acid composition

Abstract

Metabolism of long-chain fatty acids is impaired in both fasting and diabetes mellitus. A decrease in insulin activity simultaneously reduces the activity of the delta-9, delta-6, and delta-5 desaturases with respect to fatty acids either synthesized by the animal (palmitic and stearic acids) or dietarily essential (linoleic and alpha-linolenic acids). Insulin therapy corrects this defect and directly influences the level of the desaturase proteins, not only controlling the synthesis of new desaturase enzyme but also stabilizing the existing enzyme by a mechanism that is not yet understood. Although in general changes in tissue fatty acid composition are usually thought to reflect such a condition of altered desaturase activity, in diabetes there is no simple relation between the changes in desaturase activity and the changes in fatty acid composition. Fatty acid composition depends not only on desaturation/elongation but also on other interacting aspects of lipid metabolism including oxidation, substrate availability, acyl exchange, and prostanoid synthesis, as well as dietary and hormonal status. The frequent nonagreement between desaturase data and fatty acid composition in diabetes suggests that these other factors play as important a role in determining the effects of diabetes on fatty acid composition as does impaired desaturation/elongation. Further work is necessary to understand and resolve the apparent discrepancies between altered activity of enzymes controlling metabolism of long-chain fatty acids and abnormal membrane phospholipid composition in diabetes.