The role of diet derived fatty acid ethanolamines on body weight control

点击翻译按钮获取中文摘要

Fatty acid ethanolamides (FAEs) represent a class of naturally occurring bioactive lipid signaling molecules derived from FA precursors. Significant roles of FAEs have been reported in fat oxidation, energy metabolism and appetite control. The FAE oleoylethanolamide (OEA), from the oleic acid (OA), is of particular interest in body weight control. OEA, synthesized in enterocytes, is a high-affinity agonist of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPAR-α). It has been demonstrated that diets high in OA rich oils increase tissue OEA levels which stimulate lipolysis, FA β-oxidation, and promote satiety. However, much less well understood is the downstream metabolic impact of varying concentrations of FAEs in tissues, and the role of dietary FA composition that generate these varying FAE levels. Particularly, identification of optimal ratios of OEA vs other FAEs in circulation and tissues need to be elucidated. Accordingly, the long-term goal is to characterize how individual FAEs work in combination to impact energy metabolism, leading to shifts in energy substrate mobilization which impact body weight and composition. Specific objectives are to (i) assess the impact of diets enriched in individual precursor FAs from conventional and novel dietary oil blends on FA and FAE levels across regions of duodenum, jejunum and ileum, as well as other tissues, and physiological parameters related to energy regulation; (ii) examine the impact of selected ratios of dietary FAs, including OA and other FA given orally, and FAEs, including OEA and others given iv, on plasma and tissue FAE levels, gene expression, and physiological parameters related to enhancement of energy expenditure, body fat reduction, and suppression of food intake in chronic and acute states; and (iii) assess lipid mediator biomarker effects of FAE actions subsequent to varying dietary FA intakes in FAE synthesis and breakdown knockout models. Objectives (i) and (ii) will be addressed using hamsters provided diets varying in FA composition or injected with FAEs using short and long term administration regimens. FAE levels and body composition and genetic regulation of PPAR-α and other lipid mediators will be assessed. Objective (iii) will be addressed using FAE knockout mouse models to explore how FAE levels respond to different dietary FA ratios, and what downstream metabolic effects occur as a result of perturbations in pathways controlling FAE metabolism. Lastly, relationships between SNP frequency, physiological response to FAEs, and expression/activity of FAE-associated transcription factors and proteins involved in lipid metabolism will be explored. It is anticipated that results from these studies will have significant practical implications for diet fat selection leading to optimal FAE ratios as a future therapeutic target for weight management and obesity treatment.