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- Title
Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity.
- Authors
Jong Han Lee; Ligen Lin; Pingwen Xu; Kenji Saito; Qiong Wei; Meadows, Adelina G.; Bongmba, Odelia Y. N.; Pradhan, Geetali; Hui Zheng; Yong Xu; Yuxiang Sun; Lee, Jong Han; Lin, Ligen; Xu, Pingwen; Saito, Kenji; Wei, Qiong; Zheng, Hui; Xu, Yong; Sun, Yuxiang
- 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.
- Subjects
GHRELIN; GLUCOSE; SOMATOTROPIN; GENE expression; ANIMAL models in research; PREVENTION of obesity; BRAIN metabolism; ANIMAL experimentation; ANIMALS; BODY temperature regulation; CALORIMETRY; CELL receptors; DIET; ENERGY metabolism; GLUCOSE tolerance tests; HYPOTHALAMUS; INGESTION; INSULIN resistance; MICE; NEURONS; OBESITY; POLYMERASE chain reaction; RESEARCH funding
- Publication
Diabetes, 2016, Vol 65, Issue 8, p2169
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-1587