Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis. Academic Article uri icon

abstract

  • Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS-R in AgRP neurons is required for ghrelin's stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO.

published proceedings

  • Int J Mol Sci

altmetric score

  • 0.5

author list (cited authors)

  • Wu, C., Bongmba, O., Yue, J., Lee, J. H., Lin, L., Saito, K., ... Sun, Y

citation count

  • 34

complete list of authors

  • Wu, Chia-Shan||Bongmba, Odelia YN||Yue, Jing||Lee, Jong Han||Lin, Ligen||Saito, Kenji||Pradhan, Geetali||Li, De-Pei||Pan, Hui-Lin||Xu, Allison||Guo, Shaodong||Xu, Yong||Sun, Yuxiang

publication date

  • April 2017