Abstract

N-acylethanolamines (NAEs), such as anandamide (AEA), are a group of endogenous lipids derived from a fatty acid linked to ethanolamine and have a wide range of biological activities, including regulation of metabolism and food intake. We hypothesized that i) NAE plasma levels are associated with levels of total free fatty acids (FFAs) and their precursor fatty acid in fasting and non-fasting conditions and ii) moderate alcohol consumption alters non-fasting NAE levels. In a fasting and non-fasting study we sampled blood for measurements of specific NAEs and FFAs. In the fasting study blood was drawn after an overnight fast in 22 postmenopausal women. In the non-fasting study blood was sampled before and frequently after a standardized lunch with beer or alcohol-free beer in 19 premenopausal women. Fasting AEA levels correlated with total FFAs (r = 0.84; p < 0.001) and arachidonic acid levels (r = 0.42; p < 0.05). Similar results were observed for other NAEs with both total FFAs and their corresponding fatty acid precursors. In addition, AEA (r = 0.66; p < 0.01) and OEA levels (r = 0.49; p <0.02) positively related with BMI. Changes over time in non-fasting AEA levels were correlated with changes in total FFA levels, both after a lunch with beer (r = 0.80; 95% confidence interval: 0.54-0.92) and alcohol-free beer (r = 0.73; 0.41-0.89). Comparable correlations were found for other NAEs, without differences in correlations of each NAE between beer and alcohol free beer with lunch. In conclusion, i) in fasting and non-fasting states circulating anandamide and other N-acylethanolamines were associated with free fatty acid levels and ii) moderate alcohol consumption does not affect non-fasting NAE levels. This suggests that similar physiological stimuli cause the release of plasma N-acylethanolamines and free fatty acids in blood. The trials are registered at ClinicalTrials.gov numbers: NCT00524550 and NCT00652405.

Highlights

  • N-acylethanolamines (NAEs) are a group of lipid mediators, derived from a fatty acid precursor linked to an ethanolamine moiety

  • This made us hypothesize that their release into plasma is regulated by similar physiological stimuli and that plasma NAE levels parallel those of total free fatty acids (FFAs) and their precursor fatty acids

  • The primary findings of this study are i) all fasting and non-fasting plasma NAEs investigated are positively associated with both serum total FFAs and their specific fatty acid precursor and ii) prolonged and acute moderate alcohol consumption does not alter non-fasting NAE levels

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Summary

Introduction

N-acylethanolamines (NAEs) are a group of lipid mediators, derived from a fatty acid precursor linked to an ethanolamine moiety. The best studied NAE is the endocannabinoid arachidonoylethanolamide (anandamide; AEA). In addition to AEA, NAEs comprise of other non-endocannabinoids such as palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and stearoylethanolamide (SEA), for which palmitic acid, oleic acid and stearic acid serve as their respective precursor fatty acids (see Figure 1 for structures). When FFA levels decline after a meal, non-fasting levels of AEA are concomitantly decreased in normal-weight subjects [8]. This made us hypothesize that their release into plasma is regulated by similar physiological stimuli and that plasma NAE levels parallel those of total FFAs and their precursor fatty acids

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