Abstract

N-Acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = -0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms.

Highlights

  • N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown

  • Consumption of diets enriched in monounsaturated fat (OA) from high-oleic canola oil (HOCO), or enriched in omega-3 fat (ALA) from flaxseed high-oleic canola oil (FXCO), resulted in elevated concentrations of plasma OEA and alpha-linolenoyl ethanolamide (ALEA), respectively

  • It has been observed that plasma and tissue levels of NAEs in hamsters are modified in response to dietary fatty acid composition and are observed to activate lipid metabolism pathways through NAE-regulated mechanisms [5]

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Summary

Introduction

N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. The global impact of obesity and its comorbidities is widespread, signaling a need to identify key metabolic targets and molecular mechanisms involved in energy balance in response to altered nutrition. One such target is the group of N-acylethanolamines (NAEs), which are endogenous chemical signaling lipids identified as regulating lipid metabolism and feeding behavior and, possibly important in the etiology of obesity [1, 2].

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