PAQR3 Has Modulatory Roles in Obesity, Energy Metabolism, and Leptin Signaling
PAQR3 Has Modulatory Roles in Obesity, Energy Metabolism, and Leptin Signaling
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PAQR3 在肥胖、能量代谢和瘦素信号传导中具有调节作用
DOI：
10.1210/en.2013-1633
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发表时间：
2013-12-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Yan
中科院分区：
文献类型：
--
作者：
Wang, Lingdi;Wang, Xiao;Chen, Yan
饮食诱导的肥胖通常与瘦素抵抗相关，瘦素信号传导减弱有助于肥胖的进展。PAQR3是孕酮和AdipoQ受体（PAQR）家族的成员，与脂联素受体具有密切同源性。我们假设PAQR 3参与肥胖和能量稳态的调节。为了解决这一假设，我们用高脂饮食（HFD）喂养Paqr3缺失的小鼠，然后进行分析以评估肥胖、肝脂肪变性、胰岛素抵抗、代谢率和瘦素信号传导。我们发现Paqr3缺失的小鼠对HFD诱导的肥胖和肝脂肪变性具有抵抗性，并伴有胰岛素抵抗和胰岛素信号转导的改善。Paqr3缺失的小鼠具有增加的能量消耗和体力活动。HFD诱导的瘦素抵抗通过Paqr3消融逆转。在下丘脑中，PAqr3的过表达降低瘦素信号传导，而Paqr3的缺失增强瘦素信号传导。总之，本研究揭示PAQR3在调节肥胖、能量代谢和瘦素信号传导中具有重要的生理功能。
Diet-induced obesity is commonly associated with leptin resistance, and attenuated leptin signaling contributes to the progression of obesity. PAQR3 is a member of the progesterone and AdipoQ receptor (PAQR) family with close homology to adiponectin receptors. We hypothesized that PAQR3 is implicated in the regulation of obesity and energy homeostasis. To address this hypothesis, we fed Paqr3-deleted mice with high-fat diet (HFD), followed by analyses to evaluate obesity, hepatic steatosis, insulin resistance, metabolic rate, and leptin signaling. We found that mice with deletion of Paqr3 are resistant to HFD-induced obesity and hepatic steatosis, accompanied by improvement of insulin resistance and insulin signaling. Paqr3-deleted mice have an increased energy expenditure and physical activity. HFD-induced leptin resistance is reversed by Paqr3 ablation. Overexpression of PAQR3 reduces leptin signaling whereas deletion of Paqr3 enhances leptin signaling in the hypothalamus. In conclusion, this study reveals that PAQR3 has an important physiological function in modulating obesity, energy metabolism, and leptin signaling.