@article{fbc7c54232e5497a9b0cdc9655243765,
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",
note = "Funding Information: We would like to thank the technical director (Jamie Soto) and staff members of the Metabolic Phenotyping Core facility at the University of Iowa for all the services provided. We would also like to thank Teresa Ruggle for designing our graphic pictures, as well as Kristina Greiner and Paul Casella for their critical review of the manuscript. M.M. is supported by funds from the VA Merit Review Program ( I01 BX004774-01 ), the American Gastroenterological Association Gut Microbiome Pilot Research Program ( 18185800 BR01 ), the Department of Internal Medicine at University of Iowa Carver College of Medicine , and the University of Iowa Fraternal Order of Eagles Diabetes Research Center . K.R. is supported by funds from the NIH ( HL084207 ), the American Heart Association ( 14EIA18860041 ), and the University of Iowa Fraternal Order of Eagles Diabetes Research Center . D.C. is supported by funds from Cedars-Sinai Institutional Support funds. J.L.G. is supported by funds from NIH ( HL134850 and HL084207 to J.L.G.), the MCW CSTI “Obesity” Ensemble ( UL1TR001436 ), the American Heart Association ( 18EIA33890055 to J.L.G.), and the Advancing a Healthier Wisconsin endowment. M.L.G. is supported by funds from INSERM . L.V.Z. is supported by funds from the NIH ( NDK092412 ) and the VA Merit Review Program ( 1I0BX000718 ). L.R.-P. is supported by a PhD program from “Fondation pour la Recherche M{\'e}dicale” and Andr{\'e} Bado by “Fonds d{\textquoteright}Aide {\`a} la Recherche et {\`a} l{\textquoteright}Evaluation en h{\'e}pato-gastroent{\'e}rologie” (FARE). R.A.R. and C.M.L.B. were supported through an institutional T35 ( HL007485 ). M.A.E.H. is supported by research training funds from the Stead Family Department of Pediatrics at University of Iowa Carver College of Medicine . The Zeiss LSM710 in the University of Iowa{\textquoteright}s Central Microscopy Research Facilities used for confocal imaging is funded by the NIH ( 1 S10 RR025439-01 ). Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = oct,
day = "27",
doi = "10.1016/j.celrep.2020.108270",
language = "English (US)",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}