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，FAEs）是一组存在于植物和动物组织中的脂质信号分子。最近有研究表明，FAEs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。FAEs的合成涉及一系列酶修饰常见的饲粮脂肪酸。本研究的目标是：(1)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；(2)确定和比较外源性（即膳食）和内源性（即静脉注射）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单独和联合影响；（iii）确定和比较外源性和内源性FEAs对脂质和能量代谢以及饱腹感的生理表现的单独和联合影响；（iv）研究贡献基因和后续蛋白质在不同组织中FEA分解代谢的相关程度；(v)识别与faes诱导的与脂质/胆固醇代谢和饱腹感相关的基因和生理功能调节的反应性差异相对应的基因变异。仓鼠和小鼠缺乏合成或分解FAEs的酶。在最后的实验中，沿着基因的点突变频率将与大鼠模型中fae的生理反应以及fae相关转录因子和参与脂质和能量代谢的蛋白质的表达/活性相关。确定FAEs的组织水平与生理参数（如能量和脂质代谢）之间的关系，将有助于了解各种FAEs的精确调节功能。预计这些研究的结果将有助于我们通过评估作用机制来了解膳食FA选择对FEAs的调节。

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.