Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have not yet been identified. In the present study, we found the putative transient receptor potential C (TRPC) channels mediate the activation of a subpopulation of POMC neurons by mCPP (a 5-HT2CR agonist). Interestingly, mCPP-activated POMC neurons were found to be a distinct population from those activated by leptin. Together, our data suggest that 5-HT2CR and leptin receptors are expressed by distinct subpopulations of arcuate POMC neurons and that both 5-HT and leptin exert their actions in POMC neurons via TRPC channels.
Bibliographical noteFunding Information:
We thank Dr. Jefferey Friedman (Rockefeller University) for kindly providing us with the LepR-cre mice. This work was supported by grants to J.-W.S. (American Diabetes Association), Y.X. (R00DK085330, P30DK079638-03, American Diabetes Association, and the Naman Family Fund for Basic Research and the Curtis Hankamer Basic Research Fund), K.W. (R01MH061933, P50DA011806), K.W.W. (K01DK087780), and J.K.E. (R01DK53301, R01DK088423, and RL1DK081185). This work was also supported by PL1 DK081182 and UL1RR024923.