Role of fatty acid ethanolamides in regulation of energy and lipid metabolism

脂肪酸乙醇酰胺（也称为N-酰基乙醇胺，FAE）是在植物和动物组织中发现的一组脂质信号分子。最近已经表明，FAE控制能量消耗和食物摄入，然而，这些控制过程发生的机制仍然知之甚少。FAE的合成涉及一系列酶修饰常见的膳食脂肪酸（FA）。本研究的目的是（i）确定不同膳食FA摄入量对血液和组织中内源性FEAs水平的影响，（ii）确定和比较外源性FA的单独和联合作用，（即饮食）和内源性（即静脉内）FEAs对调节脂质和能量代谢的细胞调节因子的表达和活性的影响，（iii）确定和比较外源和内源FEA对脂质和能量代谢以及饱腹感的生理表现的单独和组合作用，（iv）研究贡献基因和随后的蛋白质与各种组织中的FEA代谢相关的程度，和（v）鉴定基因中的变异，所述变异对应于对FAEs诱导的基因调节和与脂质/胆固醇代谢和饱腹感相关的生理功能的响应性的差异。 将使用缺乏合成或分解FAE的酶的仓鼠和小鼠。在最后的实验中，在大鼠模型中，基因沿着的点突变的频率将与对FAE的生理反应以及参与脂质和能量代谢的FAE相关转录因子和蛋白质的表达/活性相关。 FAE的组织水平和生理参数，如包括能量和脂质代谢之间的关联的识别将提供洞察各种FAE的精确调节功能。 预计这些研究中产生的结果将有助于我们通过评估作用机制，从根本上理解通过膳食FA选择调节FEAs。

Fatty acid ethanolamides (also termed N-acylethanolamines, FAEs) are a group of lipid signalling molecules found within plants and animal tissues. Recently it has been shown that FAEs control both energy expenditure and food intake, however, the mechanisms through which these control processes occur remain poorly understood. Synthesis of FAEs involves serial enzymes modifying common dietary fatty acids (FA). The goals of the present research are to (i) determine the effects of varying dietary intakes of dietary FA on endogenous levels of FEAs in blood and tissues, (ii) determine and compare the exclusive and combinative effects of exogenous (i.e. dietary) and endogenous (i.e. intravenous) FEAs on the expression and activity of cellular regulatory factors that modulate lipid and energy metabolism, (iii) determine and compare the exclusive and combinative effects of exogenous and endogenous FEAs on physiological manifestations of lipid and energy metabolism as well as satiety, (iv) investigate the extent to which contribution genes and subsequent proteins are relevant for the FEA catabolism across various tissues, and (v) identify variations in genes that correspond to differences in responsiveness to FAEs-induced modulation of genes and physiological functions associated with lipid/cholesterol metabolism and satiety. Hamsters and mice lacking enzymes that either synthesize or break down FAEs will be used. In the final experiment, the frequency of point mutations along the gene will be associated with physiological response to FAEs and the expression/activity of FAE-associated transcription factors and proteins involved in lipid and energy metabolism in a rat model. Identification of associations between tissue levels of FAEs and physiological parameters such including energy and lipid metabolism will provide insight as to the precise regulatory functions of various FAEs. It is anticipated that results generated in these studies will be helpful in contributing to our fundamental understanding of the modulation of FEAs through dietary FA selection by assessment of the mechanism of actions.