Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity Academic Article uri icon

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.

altmetric score

  • 39.05

author list (cited authors)

  • Lee, J. H., Lin, L., Xu, P., Saito, K., Wei, Q., Meadows, A. G., ... Sun, Y.

citation count

  • 49

complete list of authors

  • Lee, Jong Han||Lin, Ligen||Xu, Pingwen||Saito, Kenji||Wei, Qiong||Meadows, Adelina G||Bongmba, Odelia YN||Pradhan, Geetali||Zheng, Hui||Xu, Yong||Sun, Yuxiang

publication date

  • May 2016