Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass. Cell Rep 2020 Oct 27;33(4):108270
Date
10/29/2020Pubmed ID
33113371Pubmed Central ID
PMC7660289DOI
10.1016/j.celrep.2020.108270Scopus ID
2-s2.0-85094561791 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
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.
Author List
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 MAuthor
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsEndocannabinoids
Female
Gastric Bypass
Humans
Male
Mice
Sympathetic Nervous System
