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

V. P. Chen, Y. Gao, L. Geng, William Stephen Brimijoin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: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.Methods: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.Results:Circulating ghrelin levels dropped substantially in the KO mice after i.v. AAV-BChE delivery, which led to normal food intake and healthy body weight. BChE KO mice that received AAV-BChE through i.v. and i.c. combined treatments not only resisted weight gain on high-fat diet but also retained normal glucose and insulin tolerance.Conclusions:These data indicate a central role for BChE in regulating both insulin and glucose homeostasis. BChE gene transfer could be a useful therapy for complications linked to diet-induced obesity and insulin resistance.

Original languageEnglish (US)
Pages (from-to)1413-1419
Number of pages7
JournalInternational Journal of Obesity
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Butyrylcholinesterase
Ghrelin
Homeostasis
Eating
Glucose
Knockout Mice
Dependovirus
High Fat Diet
Obesity
Insulin Resistance
Insulin
Weight Gain
Body Weight
Brain
Hyperinsulinism
Body Composition
Energy Intake
Intravenous Injections
Genes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis. / Chen, V. P.; Gao, Y.; Geng, L.; Brimijoin, William Stephen.

In: International Journal of Obesity, Vol. 41, No. 9, 01.09.2017, p. 1413-1419.

Research output: Contribution to journalArticle

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