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

Oct 29, 2020

Contributor: 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

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

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.
Published by Elsevier Inc.

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About The Expert

Yuanchao Ye

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Marwa Abu El Haija

Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Stanford University School of Medicine, Palo Alto, CA 94304, USA.

Donald A Morgan

Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Deng Guo

Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Yang Song

College of Pharmacy, China Medical University, 77 Puhe Rd., Liaoning 110122, P.R. China.

Aaron Frank

The Biomedical Research Department, Diabetes and Obesity Research Division, Cedars Sinai Medical Center, Beverly Hills, CA 90048, USA.

Liping Tian

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.

Ruth A Riedl

Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Colin M L Burnett

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Zhan Gao

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Zhiyong Zhu

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Shailesh K Shahi

Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Kasra Zarei

Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Anne Couvelard

INSERM U1149, Centre de Recherche sur l’Inflammation, Université de Paris, Paris 75018, France; Department of Pathology, Bichat Hospital, AP-HP, Paris 75018, France.

Nicolas Poté

INSERM U1149, Centre de Recherche sur l’Inflammation, Université de Paris, Paris 75018, France; Department of Pathology, Bichat Hospital, AP-HP, Paris 75018, France.

Lara Ribeiro-Parenti

INSERM U1149, Centre de Recherche sur l’Inflammation, Université de Paris, Paris 75018, France; Department of General and Digestive Surgery, Bichat Hospital, AP-HP, Paris 75018, France.

André Bado

INSERM U1149, Centre de Recherche sur l’Inflammation, Université de Paris, Paris 75018, France.

Lama Noureddine

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Andrew Bellizzi

Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Paul Kievit

Division of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.

Ashutosh K Mangalam

Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology and Molecular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Leonid V Zingman

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Orders of Eagles Diabetes Research Center, Iowa City, IA 52242, USA; Veterans Affairs Health Care System, Iowa City, IA 52242, USA; Obesity Research & Education Initiative, University of Iowa, Iowa City, IA 52242, USA.

Maude Le Gall

INSERM U1149, Centre de Recherche sur l’Inflammation, Université de Paris, Paris 75018, France.

Justin L Grobe

Departments of Physiology and Biomedical Engineering, Medical College of Wisconsin, Milwaukee, MI 53226, USA.

Lee M Kaplan

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Obesity, Metabolism, and Nutrition Institute, Massachusetts General Hospital, Boston, MA 02114, USA.

Deborah Clegg

College of Nursing and Health Professions, Drexel University, 1601 Cherry Street, Philadelphia, PA 19102, USA.

Kamal Rahmouni

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Orders of Eagles Diabetes Research Center, Iowa City, IA 52242, USA; Veterans Affairs Health Care System, Iowa City, IA 52242, USA; Obesity Research & Education Initiative, University of Iowa, Iowa City, IA 52242, USA.

Mohamad Mokadem

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Orders of Eagles Diabetes Research Center, Iowa City, IA 52242, USA; Veterans Affairs Health Care System, Iowa City, IA 52242, USA; Obesity Research & Education Initiative, University of Iowa, Iowa City, IA 52242, USA. Electronic address: mohamad-mokadem@uiowa.edu.

References

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