Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin.
Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin.
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DOI：
10.1016/j.metabol.2012.03.015
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发表时间：
2012-10
影响因子：
9.8
通讯作者：
Conti, Bruno
中科院分区：
文献类型：
--
作者：
Dubins, Jeffrey S.;Sanchez-Alavez, Manuel;Zhukov, Victor;Sanchez-Gonzalez, Alejandro;Moroncini, Gianluca;Carvajal-Gonzalez, Santos;Hadcock, John R.;Bartfai, Tamas;Conti, Bruno
关键词：
G蛋白偶联受体83（GPR 83）最近被证实存在于下丘脑视前区（POA）的温敏神经元（WSN）中，参与温度稳态。因此，我们研究了GPR 83是否可能通过减少其在POA中的表达来调节核心体温（CBT）。以热的形式消耗能量是哺乳动物能量消耗的主要模式，并最终影响能量稳态。因此，我们还测量了代谢的重要调节剂的水平。通过慢病毒短发夹RNA（shGPR 83）载体获得GPR 83的下调，所述载体针对其在体外降低GPR 83水平的能力而设计和选择。小鼠接受shGPR 83或非沉默载体的POA注射，并监测CBT、运动活动、食物摄入体重和IGF-1、胰岛素、瘦素和脂联素的循环水平。POA中GPR 83的下调导致在一天的黑暗/活动周期期间CBT的小（0.15°C）但显著的降低。体温降低后，体重增加，与热量摄入无关。shGPR 83小鼠还具有增加的循环脂联素水平（31916 ± 952 pg/ml对23474 ± 1507 pg/ml，p<0.01），而胰岛素、IGF-1或瘦素没有观察到变化。GPR 83可能参与中枢体温调节和循环脂联素的中枢调控。需要进一步的工作来确定GPR 83如何影响POA WSN以及它下调的长期代谢后果是什么。
The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. D issipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916 ± 952 pg/ml vs. 23474 ± 1507 pg/ml, p<0.01) while no change was observed for insulin, IGF-1 or leptin. GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of it down-regulation.
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影响因子：
2.9
作者：
Grillo, C. A.;Tamashiro, K. L.;Reagan, L. P.
通讯作者：
Reagan, L. P.
影响因子：
56.9
作者：
Conti, Bruno;Sanchez-Alavez, Manuel;Bartfai, Tamas
通讯作者：
Bartfai, Tamas
影响因子：
5.3
作者：
HARRIGAN, MT;BAUGHMAN, G;BOURGEOIS, S
通讯作者：
BOURGEOIS, S
影响因子：
--
作者：
HARRIGAN, MT;CAMPBELL, NF;BOURGEOIS, S
通讯作者：
BOURGEOIS, S
影响因子：
7.7
作者：
Duncan, BB;Schmidt, MI;Heiss, G
通讯作者：
Heiss, G