Role of Endocannabinoids in Energy-Balance Regulation in Participants in the Postobese State-a PREVIEW Study

J Clin Endocrinol Metab. 2020 Jul 1;105(7):e2511-e2520. doi: 10.1210/clinem/dgaa193.


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

Objective: 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.

Results: 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.

Conclusions: 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.

Keywords: adiposity; endocannabinoids; energy balance; protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adult
  • Aged
  • Aldehydes / blood*
  • Arachidonic Acids / blood*
  • Body Mass Index
  • Endocannabinoids / blood*
  • Energy Metabolism / physiology*
  • Female
  • Humans
  • Male
  • Meals
  • Middle Aged
  • Obesity / metabolism
  • Oleic Acids / blood*
  • Polyunsaturated Alkamides / blood*
  • Pregnenolone / blood*


  • Aldehydes
  • Arachidonic Acids
  • Endocannabinoids
  • Oleic Acids
  • Polyunsaturated Alkamides
  • oleoylethanolamide
  • Pregnenolone
  • anandamide
  • hexadecanal

Associated data