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; Zhiyong Zhu; Shailesh K. Shahi; Kasra Zarei; Anne Couvelard; Nicolas Poté; Lara Ribeiro-Parenti; André Bado; Lama Noureddine; Andrew Bellizzi; Paul Kievit; Ashutosh K. Mangalam; Leonid V. Zingman; Maude Le Gall; Justin L. Grobe; Lee M. Kaplan; Deborah Clegg; Kamal Rahmouni; Mohamad Mokadem

doi:10.1016/j.celrep.2020.108270

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, Zhiyong Zhu, Shailesh K. Shahi, Kasra Zarei, Anne Couvelard, Nicolas Poté, Lara Ribeiro-Parenti, André Bado, Lama Noureddine, Andrew Bellizzi, Paul KievitAshutosh K. Mangalam, Leonid V. Zingman, Maude Le Gall, Justin L. Grobe, Lee M. Kaplan, Deborah Clegg, Kamal Rahmouni, Mohamad Mokadem

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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.

Original language	English (US)
Article number	108270
Journal	Cell Reports
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2020.108270
State	Published - Oct 27 2020

Keywords

endocannabinoid receptor-1
energy expenditure
gastric bypass
obesity
resting metabolic rate
sleeve gastrectomy
sympathetic nervous system
thermogenesis

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2020.108270

Cite this

Ye, Y., Abu El Haija, M., Morgan, D. A., Guo, D., Song, Y., Frank, A., Tian, L., Riedl, R. A., Burnett, C. M. L., Gao, Z., Zhu, Z., Shahi, S. K., Zarei, K., Couvelard, A., Poté, N., Ribeiro-Parenti, L., Bado, A., Noureddine, L., Bellizzi, A., ... Mokadem, M. (2020). Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass. Cell Reports, 33(4), Article 108270. https://doi.org/10.1016/j.celrep.2020.108270

Ye, Y, Abu El Haija, M, Morgan, DA, Guo, D, Song, Y, Frank, A, Tian, L, Riedl, RA, Burnett, CML, Gao, Z, Zhu, Z, Shahi, SK, Zarei, K, Couvelard, A, Poté, N, Ribeiro-Parenti, L, Bado, A, Noureddine, L, Bellizzi, A, Kievit, P, Mangalam, AK, Zingman, LV, Le Gall, M, Grobe, JL, Kaplan, LM, Clegg, D, Rahmouni, K & Mokadem, M 2020, 'Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass', Cell Reports, vol. 33, no. 4, 108270. https://doi.org/10.1016/j.celrep.2020.108270

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

abstract = "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.",

keywords = "endocannabinoid receptor-1, energy expenditure, gastric bypass, obesity, resting metabolic rate, sleeve gastrectomy, sympathetic nervous system, thermogenesis",

author = "Yuanchao Ye and {Abu El Haija}, Marwa and Morgan, {Donald A.} and Deng Guo and Yang Song and Aaron Frank and Liping Tian and Riedl, {Ruth A.} and Burnett, {Colin M.L.} and Zhan Gao and Zhiyong Zhu and Shahi, {Shailesh K.} and Kasra Zarei and Anne Couvelard and Nicolas Pot{\'e} and Lara Ribeiro-Parenti and Andr{\'e} Bado and Lama Noureddine and Andrew Bellizzi and Paul Kievit and Mangalam, {Ashutosh K.} and Zingman, {Leonid V.} and {Le Gall}, Maude and Grobe, {Justin L.} and Kaplan, {Lee M.} and Deborah Clegg and Kamal Rahmouni and Mohamad Mokadem",

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AU - Ye, Yuanchao

AU - Abu El Haija, Marwa

AU - Morgan, Donald A.

AU - Guo, Deng

AU - Song, Yang

AU - Frank, Aaron

AU - Tian, Liping

AU - Riedl, Ruth A.

AU - Burnett, Colin M.L.

AU - Gao, Zhan

AU - Zhu, Zhiyong

AU - Shahi, Shailesh K.

AU - Zarei, Kasra

AU - Couvelard, Anne

AU - Poté, Nicolas

AU - Ribeiro-Parenti, Lara

AU - Bado, André

AU - Noureddine, Lama

AU - Bellizzi, Andrew

AU - Kievit, Paul

AU - Mangalam, Ashutosh K.

AU - Zingman, Leonid V.

AU - Le Gall, Maude

AU - Grobe, Justin L.

AU - Kaplan, Lee M.

AU - Clegg, Deborah

AU - Rahmouni, Kamal

AU - Mokadem, Mohamad

PY - 2020/10/27

Y1 - 2020/10/27

N2 - 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.

AB - 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.

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KW - energy expenditure

KW - gastric bypass

KW - obesity

KW - resting metabolic rate

KW - sleeve gastrectomy

KW - sympathetic nervous system

KW - thermogenesis

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JO - Cell Reports

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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