Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis.

International Journal of Obesity : Journal of the International Association for the Study of Obesity
V P ChenS Brimijoin

Abstract

Ghrelin is the only orexigenic hormone known to stimulate food intake and promote obesity and insulin resistance. We recently showed that plasma ghrelin is controlled by butyrylcholinesterase (BChE), which has a strong impact on feeding and weight gain. BChE knockout (KO) mice are prone to obesity on high-fat diet, but hepatic BChE gene transfer rescues normal food intake and obesity resistance. However, these mice lack brain BChE and still develop hyperinsulinemia and insulin resistance, suggesting essential interactions between BChE and ghrelin within the brain. To test the hypothesis we used four experimental groups: (1) untreated wild-type mice, (2) BChE KO mice with LUC delivered by adeno-associated virus (AAV) in combined intravenous (i.v.) and intracerebral (i.c.) injections, (3) KO mice given AAV for mouse BChE (i.v. only) and (4) KO mice given the same vector both i.v. and i.c. All mice ate a 45% calorie high-fat diet from the age of 1 month. Body weight, body composition, daily caloric intake and serum parameters were monitored throughout, and glucose tolerance and insulin tolerance tests were performed at intervals. Circulating ghrelin levels dropped substantially in the KO mice after i.v. AAV-BChE delivery, which le...Continue Reading

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Citations

Dec 24, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Natacha GermainBogdan Galusca
Mar 16, 2019·Endocrinology·Bharath K ManiJeffrey M Zigman
Jun 23, 2020·Expert Opinion on Therapeutic Patents·Jacob E MooseJames L Hougland
Nov 19, 2020·Biomolecules·Hafsa Amat-Ur-RasoolWayne G Carter
Feb 8, 2018·Biochemical Pharmacology·Carey N Pope, Stephen Brimijoin
Mar 2, 2021·Molecular Metabolism·Yuguang ZhaoE Yvonne Jones
Nov 28, 2020·Molecular Metabolism·Deepali GuptaJeffrey M Zigman

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Methods Mentioned

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