TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

Yong Gao, Ting Yao, Zhuo Deng, Jong Woo Sohn, Jia Sun, Yiru Huang, Xingxing Kong, Kai jiang Yu, Rui tao Wang, Hong Chen, Hongbo Guo, Jianqun Yan, Kathryn A. Cunningham, Yongsheng Chang, Tiemin Liu, Kevin W. Williams

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.

Original languageEnglish (US)
Pages (from-to)583-592
Number of pages10
JournalCell Reports
Volume18
Issue number3
DOIs
StatePublished - Jan 17 2017

Keywords

  • diabetes
  • electrophysiology
  • glycemia
  • leptin
  • lorcaserin
  • melanocortin
  • obesity
  • patch-clamp
  • serotonin
  • thermogenesis
  • transient receptor potential cation channels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Gao, Y., Yao, T., Deng, Z., Sohn, J. W., Sun, J., Huang, Y., Kong, X., Yu, K. J., Wang, R. T., Chen, H., Guo, H., Yan, J., Cunningham, K. A., Chang, Y., Liu, T., & Williams, K. W. (2017). TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons. Cell Reports, 18(3), 583-592. https://doi.org/10.1016/j.celrep.2016.12.072