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

Authors

[:fr]Yuanchao Ye[:],

[:fr]Marwa Abu El Haija[:],

[:fr]Donald A Morgan[:],

[:fr]Deng Guo[:],

[:fr]Yang Song[:],

[:fr]Aaron Frank[:],

[:fr]Liping Tian[:],

[:fr]Ruth A Riedl[:],

[:fr]Colin M L Burnett[:],

[:fr]Zhan Gao[:],

[:fr]Zhiyong Zhu[:],

[:fr]Shailesh K Shahi[:],

[:fr]Kasra Zarei[:],

Couvelard Anne,

Poté Nicolas,

Ribeiro-Parenti Lara,

Bado André,

[:fr]Lama Noureddine[:],

[:fr]Andrew Bellizzi[:],

[:fr]Paul Kievit[:],

[:fr]Ashutosh K Mangalam[:],

[:fr]Leonid V Zingman[:],

Le Gall Maude,

[:fr]Justin L Grobe[:],

[:fr]Lee M Kaplan[:],

[:fr]Deborah Clegg[:],

[:fr]Kamal Rahmouni[:],

[:fr]Mohamad Mokadem[:],

[:en]

Bariatric surgery and differences in the regulation of basal metabolism

In an article published in the journal Cell Reports (October 2020), the PIMS research team, led by Maude Le Gall and André Bado, shows that the regulation of the basic metabolism of the operated obese patient differs according to the bariatric surgery used: the gastric bypass known as “of the Roux-en-Y type” (RYGB) or the sleeve gastrectomy (SG). This work was carried out in collaboration with researchers from the University of Iowa (USA).

Currently, there are few or no effective pharmacological and behavioral therapies for the management of severe obesity. Bariatric surgery remains the most effective treatment, with RYGB (standard procedure) and SG being the most used techniques. In addition to weight loss and its long-term maintenance, RYGB and SG improve dyslipidemia, non-alcoholic fatty liver disease, and type 2 diabetes in operated patients, sometimes even before weight loss. However, the mechanisms underlying these beneficial effects are complex and remain debated.

In this study, researchers demonstrated, using a combination of direct and indirect calorimetry, an increase in basal metabolism, in particular its anaerobic component after RYGB, but not after SG. This increase was associated with a specific increase in splanchnic sympathetic nerve activity and “browning” of the mesenteric adipose tissue.

Among their main observations:

Selective splanchnic denervation suppresses all beneficial effects of RYGB by mechanisms involving endocannabinoid signaling in the small intestine.
Administration of an endocannabinoid-1 (CB1) receptor antagonist to obese mice mimics the specific effects of RYGB surgery on metabolism, while that of a CB1 agonist attenuates its effects.

These results identify the CB1 receptor as an important player in basal metabolism after RYGB surgery via a pathway involving the sympathetic nervous system. This receptor could therefore represent a therapeutic target of interest for the treatment of obesity associated with type 2 diabetes.

Cell Rep. 2020 33 (4): 108270. doi: 10.1016