Sex Differences in Fatty Acid Metabolism

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Fatty acids in blood and tissues are different in women and men. The long term of the present research is to determine the sex differences in fatty acid metabolism that result in different levels of docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acids and differences in levels of n-7 to n-9 monounsaturated fatty acids in humans and we have confirmed these differences in rodent models. We will examine various factors that control the levels of fatty acids including fatty acid synthesis, fatty acid incorporation into complex lipids, fatty acid oxidation and diet. In the rodent models, we have observed sex differences in the expression of genes involved in the synthesis of these fatty acids, but the role of sex hormones such as estrogen in the control of this expression is not by direct activation. Therefore, we will examine sex differences in lipogenesis pathways to identify sex hormone interactions that might be indirectly activating DHA and n-7 monounsaturated fatty acid synthesis in rodents and in cell culture models. In particular, we will be examining the role of estrogen on the synthesis of phospholipids for cell membranes, and the synthesis of triacylglycerols for energy storage. We expect that the sex differences in fatty acid synthesis mainly occur in the liver and that estrogen is transactivating liver X receptor response elements that increases desaturation and elongation of fatty acids through changes in pathways involving sterol regulatory element binding protein-1c, peroxisome proliferator activated receptor a, and carbohydrate responsive element binding protein. The understanding gained from this research can provide insight on sex differences in various systems in human and animal physiology and on fatty acid uptake and incorporation. For example, sex differences in n-7 monounsaturated fatty acids metabolism my partially explain sex difference in insulin sensitivity. A greater understanding of the metabolism and biosynthesis of n-3 polyunsaturated fatty acids is critical to determine nutritional requirements in humans, and to assist in strategies to increase n-3 polyunsaturated fatty acids in the food supply.