Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans

J Lipid Res. 2014 Dec;55(12):2655-64. doi: 10.1194/jlr.P051235. Epub 2014 Sep 28.


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.

Trial registration: NCT00927199.

Keywords: arachidonoylethanolamide; body composition; canola oil; clinical trials; endocannabinoids; fatty acid metabolism; fatty acid oxidation; oleic acid; oleoylethanolamide; peroxisome proliferator-activated receptor.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Adult
  • Body Mass Index
  • Cohort Studies
  • Cross-Over Studies
  • Dietary Fats / metabolism*
  • Endocannabinoids / blood*
  • Endocannabinoids / metabolism
  • Energy Metabolism*
  • Fatty Acids, Monounsaturated / metabolism
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / metabolism*
  • Linseed Oil / metabolism
  • Male
  • Middle Aged
  • Oleic Acids / blood*
  • Oleic Acids / metabolism
  • Overweight / physiopathology*
  • Oxidation-Reduction
  • Patient Dropouts
  • Polyunsaturated Alkamides / blood*
  • Polyunsaturated Alkamides / metabolism
  • Rapeseed Oil
  • Single-Blind Method
  • Up-Regulation*


  • Dietary Fats
  • Endocannabinoids
  • Fatty Acids, Monounsaturated
  • Oleic Acids
  • Polyunsaturated Alkamides
  • Rapeseed Oil
  • alpha-linolenoyl ethanolamide
  • oleoylethanolamide
  • Linseed Oil

Associated data