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Front Endocrinol (Lausanne). 2021 Aug 09;12:716431. doi: 10.3389/fendo.2021.716431. eCollection 2021.

Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human.

Frontiers in endocrinology

Chloé Buch, Tania Muller, Julia Leemput, Patricia Passilly-Degrace, Pablo Ortega-Deballon, Jean-Paul Pais de Barros, Bruno Vergès, Tony Jourdan, Laurent Demizieux, Pascal Degrace

Affiliations

  1. Team Pathophysiology of Dyslipidemia, INSERM UMR1231, Université de Bourgogne Franche-Comté, Dijon, France.
  2. Department of Digestive, Thoracic and Surgical Oncology, University Hospital, Dijon, France.
  3. Lipidomic Platform, INSERM UMR1231, Université de Bourgogne Franche-Comté, Dijon, France.
  4. Department of Endocrinology-Diabetology, University Hospital, Dijon, France.

PMID: 34434170 PMCID: PMC8382141 DOI: 10.3389/fendo.2021.716431

Abstract

White adipose tissue (WAT) possesses the endocannabinoid system (ECS) machinery and produces the two major endocannabinoids (ECs), arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). Accumulating evidence indicates that WAT cannabinoid 1 receptors (CB1R) are involved in the regulation of fat storage, tissue remodeling and secretory functions but their role in controlling lipid mobilization is unclear. In the present study, we used different strategies to acutely increase ECS activity in WAT and tested the consequences on glycerol production as a marker of lipolysis. Treating lean mice or rat WAT explants with JLZ195, which inhibits ECs degrading enzymes, induced an increase in 2-AG tissue contents that was associated with a CB1R-dependent decrease in lipolysis. Direct treatment of rat WAT explants with AEA also inhibited glycerol production while mechanistic studies revealed it could result from the stimulation of Akt-signaling pathway. Interestingly, AEA treatment decreased lipolysis both in visceral and subcutaneous WAT collected on lean subjects suggesting that ECS also reduces fat store mobilization in Human. In obese mice, WAT content and secretion rate of ECs were higher than in control while glycerol production was reduced suggesting that over-produced ECs may inhibit lipolysis activating local CB1R. Strikingly, our data also reveal that acute CB1R blockade with Rimonabant did not modify lipolysis

Copyright © 2021 Buch, Muller, Leemput, Passilly-Degrace, Ortega-Deballon, Pais de Barros, Vergès, Jourdan, Demizieux and Degrace.

Keywords: Akt; adipose tissue; cAMP; cannabinoid (CB) receptor 1; endocannabinoid system (ECS); hormono-sensible lipase; lipolysis and fatty acid metabolism; obesity

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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