Roles of Endocannabinoids and Endocannabinoid-Like Molecules in Energy Homeostasis and Metabolic Regulation: A Nutritional Perspective

Annu Rev Nutr. 2021 Oct 11;41:177-202. doi: 10.1146/annurev-nutr-043020-090216. Epub 2021 Jun 11.


The endocannabinoid system is involved in signal transduction in mammals. It comprises principally G protein-coupled cannabinoid receptors and their endogenous agonists, called endocannabinoids, as well as the enzymes and transporters responsible for the metabolism of endocannabinoids. Two arachidonic acid-containing lipid molecules, arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol, function as endocannabinoids. N-acylethanolamines and monoacylglycerols, in which the arachidonic acid chain is replaced with a saturated or monounsaturated fatty acid, are not directly involved in the endocannabinoid system but exhibit agonistic activities for other receptors. These endocannabinoid-like moleculesinclude palmitoylethanolamide, oleoylethanolamide (OEA), and 2-oleoylglycerol. Endocannabinoids stimulate feeding behavior and the anabolism of lipids and glucose, while OEA suppresses appetite. Both central and peripheral systems are included in these nutritional and metabolic contexts. Therefore, they have potential in the treatment and prevention of obesity. We outline the structure, metabolism, and biological activities of endocannabinoids and related molecules, and focus on their involvement in energy homeostasis and metabolic regulation.

Keywords: 2-arachidonoylglycerol; N-acylethanolamine; anandamide; appetite; oleoylethanolamide; peroxisome proliferator-activated receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endocannabinoids* / metabolism
  • Homeostasis
  • Humans
  • Mammals / metabolism
  • Obesity*


  • Endocannabinoids