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Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity
Lee J.H.1; Lin L.1,2; Xu P.1; Saito K.1; Wei Q.1,3; Meadows A.G.1; Bongmba O.Y.N.1; Pradhan G.1; Zheng H.4; Xu Y.1; Sun Y.1,4,5,6
2016
Source PublicationDiabetes
ISSN121797
Volume65Issue:8Pages:2169
Abstract

Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy. © 2016 by the American Diabetes Association.

DOI10.2337/db15-1587
URLView the original
Indexed BySCI
Language英语
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000380750400013
The Source to ArticleScopus
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Cited Times [WOS]:31   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSun Y.
Affiliation1.USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
3.Division of Endocrinology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
4.Huffington Center on Aging, Baylor College of Medicine, Houston, TX
5.Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX
6.Department of Nutrition and Food Science, Texas A&M University, College Station, TX
Recommended Citation
GB/T 7714
Lee J.H.,Lin L.,Xu P.,et al. Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity[J]. Diabetes,2016,65(8):2169.
APA Lee J.H..,Lin L..,Xu P..,Saito K..,Wei Q..,...&Sun Y..(2016).Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity.Diabetes,65(8),2169.
MLA Lee J.H.,et al."Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity".Diabetes 65.8(2016):2169.
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