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

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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.