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

脂肪酸乙醇酰胺在能量和脂质代谢调节中的作用

• 批准号: 180398-2012
• 负责人: Jones, Peter
• 金额: $ 4.74万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=545911
• 关键词: Role; fatty; acid; ethanolamides; regulation

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.

脂肪酸乙醇酰胺(又称N-酰基乙醇胺，FAE)是一组存在于动植物组织中的脂质信号分子。最近的研究表明，FAE同时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的合成涉及到一系列修饰常见膳食脂肪酸(FA)的酶。本研究的目的是：(I)确定饮食中不同的FA摄入量对血液和组织中内源性FEA水平的影响；(Ii)确定和比较外源(即膳食)和内源(即静脉)FEA对调节脂肪和能量代谢的细胞调节因子的表达和活性的独占和组合效应；(Iii)确定和比较外源和内源FEA对脂肪和能量代谢以及饱腹感的生理表现的独有和组合效应；(Iv)研究贡献基因和后续蛋白质在多大程度上与不同组织的FEA分解代谢有关，以及(V)确定基因变异，这些变异对应于对FAES诱导的基因调节的反应差异，以及与脂肪/胆固醇代谢和饱腹感相关的生理功能。缺乏合成或分解FAE的酶的仓鼠和小鼠将被使用。在最终的实验中，该基因点突变的频率将与对FAE的生理反应以及FAE相关的转录因子和蛋白质的表达/活性有关，这些转录因子和蛋白质参与了大鼠的脂肪和能量代谢。确定FAE的组织水平与包括能量和脂肪代谢在内的生理参数之间的关联将有助于深入了解各种FAE的精确调节功能。预计这些研究产生的结果将有助于我们通过评估作用机制来选择膳食FA来帮助我们从根本上理解FEA的调节。