Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue.
Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue.
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DOI：
10.1038/srep14953
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发表时间：
2015-10-12
影响因子：
4.6
通讯作者：
Kunos G
中科院分区：
文献类型：
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作者：
Godlewski G;Jourdan T;Szanda G;Tam J;Cinar R;Harvey-White J;Liu J;Mukhopadhyay B;Pacher P;Ming Mo F;Osei-Hyiaman D;Kunos G
我们报告了一个意想不到的联系之间的老化，产热和体重增加通过孤儿G蛋白偶联受体GPR3。缺乏GPR3并维持正常食物的小鼠在其生命的前5个月期间具有相似的体重，但此后体重增加得更多，并显示出总能量消耗减少和核心体温降低。到5月龄时，GPR3 KO小鼠已经具有较低的产热基因表达和解偶联蛋白1蛋白水平，并且相对于WT同窝出生的小鼠显示出肩胛间棕色脂肪组织（iBAT）的葡萄糖摄取受损。GPR3 KO小鼠iBAT中的这些分子偏差先于环境条件下体重和核心体温的可测量差异，但与急性冷挑战期间未能维持热稳态相关联。与此同时，同样的冷攻击导致WT小鼠iBAT中Gpr3表达增加17倍。因此，GPR3似乎在iBAT的产热反应中具有关键作用，并可能代表年龄相关性肥胖症的新治疗靶点。
We report an unexpected link between aging, thermogenesis and weight gain via the orphan G protein-coupled receptor GPR3. Mice lacking GPR3 and maintained on normal chow had similar body weights during their first 5 months of life, but gained considerably more weight thereafter and displayed reduced total energy expenditure and lower core body temperature. By the age of 5 months GPR3 KO mice already had lower thermogenic gene expression and uncoupling protein 1 protein level and showed impaired glucose uptake into interscapular brown adipose tissue (iBAT) relative to WT littermates. These molecular deviations in iBAT of GPR3 KO mice preceded measurable differences in body weight and core body temperature at ambient conditions, but were coupled to a failure to maintain thermal homeostasis during acute cold challenge. At the same time, the same cold challenge caused a 17-fold increase in Gpr3 expression in iBAT of WT mice. Thus, GPR3 appears to have a key role in the thermogenic response of iBAT and may represent a new therapeutic target in age-related obesity.