TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

被引：81
|
作者：
Gao, Yong [1 ,2 ,13 ]
Yao, Ting [3 ,13 ]
Deng, Zhuo [4 ,13 ]
Sohn, Jong-Woo [5 ,13 ]
Sun, Jia [6 ,13 ]
Huang, Yiru [7 ,13 ]
Kong, Xingxing [8 ,9 ]
Yu, Kai-jiang [10 ]
Wang, Rui-tao [10 ]
Chen, Hong [6 ]
Guo, Hongbo [7 ]
Yan, Jianqun [3 ]
Cunningham, Kathryn A. [11 ,12 ]
Chang, Yongsheng [1 ,2 ]
Liu, Tiemin [10 ,13 ]
Williams, Kevin W. [13 ]
机构：
[1] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
[2] Peking Union Med Coll, Beijing 100005, Peoples R China
[3] Xi An Jiao Tong Univ, Dept Physiol & Pathophysiol, Sch Med, Xian 710061, Shaanxi, Peoples R China
[4] Shaanxi Prov Peoples Hosp, Dept Gynecol, Xian 710000, Shaanxi, Peoples R China
[5] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea
[6] Southern Med Univ, Zhujiang Hosp, Dept Endocrinol, Guangzhou 510282, Guangdong, Peoples R China
[7] Southern Med Univ, Zhujiang Hosp, Dept Neurosurg, Guangzhou 510282, Guangdong, Peoples R China
[8] Harvard Univ, Div Endocrinol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[9] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA
[10] Harbin Med Univ, Affiliated Hosp 3, Dept Intens Care Unit, Harbin 150081, Peoples R China
[11] Univ Texas Med Branch, Ctr Addict Res, Galveston, TX 77555 USA
[12] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA
[13] Univ Texas Southwestern Med Ctr Dallas, Div Hypothalam Res, Dallas, TX 75390 USA
来源：
CELL REPORTS | 2017年 / 18卷 / 03期
基金：
新加坡国家研究基金会; 中国国家自然科学基金;
关键词：
HYPOTHALAMIC PROOPIOMELANOCORTIN NEURONS; REGULATES GLUCOSE-HOMEOSTASIS; ARCUATE NUCLEUS; ENERGY-BALANCE; AGRP NEURONS; INSULIN SENSITIVITY; FEEDING CIRCUITS; NEUROPEPTIDE-Y; D-FENFLURAMINE; BODY-WEIGHT;
D O I：
10.1016/j.celrep.2016.12.072
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 leptinand serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.
引用
收藏
页码：583 / 592
页数：10
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