Role of endocannabinoids in energy-balance regulation in participants in the postobese state – a PREVIEW Study


Drummen M, Tischmann L, Gatta-Cherifi B, Cota D, Matias I, Raben A, Adam T, Westerterp-Plantenga M




J Clin Endocrinol Metab . 2020 Jul 1;105(7):e2511-e2520.

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Endocannabinoids are suggested to play a role in energy balance regulation.


We aimed to investigate associations of endocannabinoid concentrations during the day with energy balance and adiposity and interactions with 2 diets differing in protein content in participants in the postobese phase with prediabetes.

Design and participants

Participants (n = 38) were individually fed in energy balance with a medium protein (MP: 15:55:30% of energy from protein:carbohydrate:fat) or high-protein diet (HP: 25:45:30% energy from P:C:F) for 48 hours in a respiration chamber.

Main outcome measures

Associations between energy balance, energy expenditure, respiratory quotient, and endocannabinoid concentrations during the day were assessed.


Plasma-concentrations of anandamide (AEA), oleoylethanolamide (OEA), palmitoyethanolamide (PEA), and pregnenolone (PREG) significantly decreased during the day. This decrease was inversely related to body mass index (AEA) or body fat (%) (PEA; OEA). The lowest RQ value, before lunch, was inversely associated with concentrations of AEA and PEA before lunch. Area under the curve (AUC) of concentrations of AEA, 2-AG, PEA, and OEA were positively related to body fat% (P < .05).The HP and MP groups showed no differences in concentrations of AEA, OEA, PEA, and PREG, but the AUC of 2-arachidonoylglycerol (2-AG) was significantly higher in the HP vs the MP group.


In energy balance, only the endocannabinoid 2-AG changed in relation to protein level of the diet, whereas the endocannabinoid AEA and endocannabinoid-related compounds OEA and PEA reflected the gradual energy intake matching energy expenditure during the day.

Trial registration NCT01777893.

Published by Oxford University Press on behalf of the Endocrine Society 2020.

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