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

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...

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Autores principales: Buch, Chloé, Muller, Tania, Leemput, Julia, Passilly-Degrace, Patricia, Ortega-Deballon, Pablo, Pais de Barros, Jean-Paul, Vergès, Bruno, Jourdan, Tony, Demizieux, Laurent, Degrace, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382141/
https://www.ncbi.nlm.nih.gov/pubmed/34434170
http://dx.doi.org/10.3389/fendo.2021.716431
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author Buch, Chloé
Muller, Tania
Leemput, Julia
Passilly-Degrace, Patricia
Ortega-Deballon, Pablo
Pais de Barros, Jean-Paul
Vergès, Bruno
Jourdan, Tony
Demizieux, Laurent
Degrace, Pascal
author_facet Buch, Chloé
Muller, Tania
Leemput, Julia
Passilly-Degrace, Patricia
Ortega-Deballon, Pablo
Pais de Barros, Jean-Paul
Vergès, Bruno
Jourdan, Tony
Demizieux, Laurent
Degrace, Pascal
author_sort Buch, Chloé
collection PubMed
description 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 in vitro in obese mice and human explants nor in vivo in obese mice. Taken together, these data provide physiological evidence that activation of ECS in WAT, by limiting fat mobilization, may participate in the progressive tissue remodeling that could finally lead to organ dysfunction. The present findings also indicate that acute CB1R blockade is inefficient in regulating lipolysis in obese WAT and raise the possibility of an alteration of CB1R signaling in conditions of obesity.
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spelling pubmed-83821412021-08-24 Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human Buch, Chloé Muller, Tania Leemput, Julia Passilly-Degrace, Patricia Ortega-Deballon, Pablo Pais de Barros, Jean-Paul Vergès, Bruno Jourdan, Tony Demizieux, Laurent Degrace, Pascal Front Endocrinol (Lausanne) Endocrinology 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 in vitro in obese mice and human explants nor in vivo in obese mice. Taken together, these data provide physiological evidence that activation of ECS in WAT, by limiting fat mobilization, may participate in the progressive tissue remodeling that could finally lead to organ dysfunction. The present findings also indicate that acute CB1R blockade is inefficient in regulating lipolysis in obese WAT and raise the possibility of an alteration of CB1R signaling in conditions of obesity. Frontiers Media S.A. 2021-08-09 /pmc/articles/PMC8382141/ /pubmed/34434170 http://dx.doi.org/10.3389/fendo.2021.716431 Text en Copyright © 2021 Buch, Muller, Leemput, Passilly-Degrace, Ortega-Deballon, Pais de Barros, Vergès, Jourdan, Demizieux and Degrace https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Buch, Chloé
Muller, Tania
Leemput, Julia
Passilly-Degrace, Patricia
Ortega-Deballon, Pablo
Pais de Barros, Jean-Paul
Vergès, Bruno
Jourdan, Tony
Demizieux, Laurent
Degrace, Pascal
Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title_full Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title_fullStr Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title_full_unstemmed Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title_short Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human
title_sort endocannabinoids produced by white adipose tissue modulate lipolysis in lean but not in obese rodent and human
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382141/
https://www.ncbi.nlm.nih.gov/pubmed/34434170
http://dx.doi.org/10.3389/fendo.2021.716431
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