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Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass
Journal article   Open access   Peer reviewed

Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass

Yuanchao Ye, Marwa Abu El Haija, Donald A. Morgan, Deng Guo, Yang Song, Aaron Frank, Liping Tian, Ruth A. Riedl, Colin M.L. Burnett, Zhan Gao, …
Cell reports (Cambridge), v 33(4), 108270
27 Oct 2020
PMID: 33113371
url
http://www.cell.com/article/S2211124720312596/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1016/j.celrep.2020.108270View
Published, Version of Record (VoR) Open

Abstract

endocannabinoid receptor-1 energy expenditure gastric bypass obesity resting metabolic rate sleeve gastrectomy sympathetic nervous system thermogenesis
The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and “browning” of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system. [Display omitted] •RYGB, but not SG, increases energy expenditure (EE) and RMR•This increase in EE is due to sympathetic-mediated “browning” of mesenteric fat•CB1 inverse agonist induces splanchnic nerve activity and fat thermogenesis•CB1 agonist attenuates the RYGB-induced weight loss and “browning” of mesenteric fat Ye et al. show that energy regulation differs between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) where only RYGB enhances splanchnic nerve activity, to induce visceral fat thermogenesis, and increases resting metabolic rate (RMR). This sympathetic-mediated “browning” of visceral fat seems to be dependent on endocannabinoid receptor-1 (CB1) signaling.

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Domestic collaboration
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Web of Science research areas
Cell Biology
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