Sex Differences in Fatty Acid Metabolism

点击翻译按钮获取中文摘要

Fatty acids in blood and tissues are different in women and men. The long term objective 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 and n-9 monounsaturated fatty acids in mammals. 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 rodent models, we have observed sex differences in the expression of genes involved in the synthesis of these fatty acids. This appears to be regulated by a direct effect of estrogen, but also indirect effects on general lipogenesis. Therefore, in addition to sex hormone effects on fatty acid synthesis, we will use lipid analytical and gene expression screening techniques (shot-gun lipidomics and gene microarrays) to identify sex differences in metabolic pathways in rodents. 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 mediates several transcription factors involved in lipid synthesis including sterol regulatory element binding protein-1c, peroxisome proliferator activated receptors, liver X receptor, and carbohydrate responsive element binding protein. We also expect to discover estrogen response elements in the promoter regions of key enzymes such as delta-6 desaturase. 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 may partially explain sex differences 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.