title: TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.
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.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Gynecology, Shaanxi Provincial People's Hospital, Shaanxi 710000, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Sohn
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA 02115, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, 150081, China.
authors.forename: Kai-Jiang
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, 150081, China.
authors.forename: Rui-Tao
authors.initials: RT
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Jianqun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Center for Addiction Research and the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Cunningham
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China. Electronic address: changy@ibms.pumc.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, 150081, China; Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA. Electronic address: tiemin.liu@utsouthwestern.edu.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA. Electronic address: kevin.williams@utsouthwestern.edu.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D001067:Appetite Depressants; D001552:Benzazepines; D020738:Leptin; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse; D013629:Tamoxifen; C506658:lorcaserin; D011333:Pro-Opiomelanocortin; D005947:Glucose
keywords: diabetes; electrophysiology; glycemia; leptin; lorcaserin; melanocortin; obesity; patch-clamp; serotonin; thermogenesis; transient receptor potential cation channels