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Cell Rep. 2017 Jan 17;18(3):583-592. doi: 10.1016/j.celrep.2016.12.072.

TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.

Author information

1
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.
2
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.
3
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.
4
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.
5
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.
6
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.
7
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA 02115, USA.
8
Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, 150081, China.
9
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
10
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
11
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China.
12
Center for Addiction Research and the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
13
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.
14
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.
15
Division of Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA. Electronic address: kevin.williams@utsouthwestern.edu.

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.

KEYWORDS:

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

PMID:
28099839
PMCID:
PMC5324780
DOI:
10.1016/j.celrep.2016.12.072
[Indexed for MEDLINE]
Free PMC Article

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