Sex Differences in Fatty Acid Metabolism

血液和组织中的脂肪酸在女性和男性中是不同的。本研究的长期目标是确定导致哺乳动物中不同水平的二十二碳六烯酸(DHA)的脂肪酸代谢的性别差异，以及n-7和n-9单不饱和脂肪酸水平的差异。我们将检查控制脂肪酸水平的各种因素，包括脂肪酸合成、脂肪酸融入复合脂质、脂肪酸氧化和饮食。在啮齿动物模型中，我们观察到参与这些脂肪酸合成的基因表达的性别差异。这似乎是由雌激素的直接作用调节的，但也对一般脂肪生成有间接影响。因此，除了性激素对脂肪酸合成的影响外，我们还将利用脂质分析和基因表达筛选技术(枪炮脂质组学和基因芯片)来识别啮齿动物代谢途径中的性别差异。特别是，我们将研究雌激素在细胞膜磷脂合成和能量储存三酰甘油合成中的作用。我们推测，脂肪酸合成的性别差异主要发生在肝脏，雌激素介导了几种参与脂肪合成的转录因子，包括类固醇调节元件结合蛋白-1c、过氧化物酶体增殖物激活受体、肝脏X受体和碳水化合物反应元件结合蛋白。我们还希望在关键酶的启动子区域发现雌激素反应元件，如Delta-6去饱和酶。从这项研究中获得的理解可以洞察人类和动物生理学中不同系统中的性别差异，以及脂肪酸的摄取和结合。例如，n-7单不饱和脂肪酸代谢的性别差异可能部分解释了胰岛素敏感性的性别差异。更好地了解n-3多不饱和脂肪酸的代谢和生物合成对于确定人类的营养需求和帮助制定增加食品供应中n-3多不饱和脂肪酸的策略至关重要。

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.