中科院上海生科院营养所陈雁研究组在一项研究中，发现并阐明了一个能够调节机体肥胖的关键分子。近日，相关研究论文在线发表于《内分泌学》。
在研究员陈雁的指导下，博士生王玲娣等深入研究了在细胞内高尔基体特异定位蛋白质PAQR3的基因缺失对高脂饮食诱导小鼠发生肥胖、肝脏脂肪变性和胰岛素抵抗等改变的影响。
研究发现，PAQR3基因缺失的小鼠可以抵抗高脂饮食诱导产生的肥胖和肝脏脂肪变性，并伴随胰岛素抵抗和胰岛素信号传导的改善。PAQR3缺失的小鼠的能量消耗和基础活动也有一定增强，同时，PAQR3的缺失可以改善高脂饮食诱导的瘦素抵抗。在下丘脑中，PAQR3过表达能抑制瘦素信号；反之，PAQR3降低则促进瘦素信号。因此，这一研究表明，PAQR3在肥胖、能量代谢以及瘦素信号的调控过程中发挥重要的生理学功能。
此前，陈雁研究组围绕PAQR3开展了一系列的研究工作，曾发现PAQR3能够招募一系列关键信号分子，调控多个关键的细胞信号通路，参与肿瘤的发生以及胰岛素敏感性的调控。
此外，由于PAQR3属于孕酮和脂联素受体（PAQR）家族的一员，与脂联素受体有很高的同源性，因此该团队曾推测PAQR3可能参与了肥胖以及能量平衡的调节过程。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Endocrinology doi: 10.1210/en.2013-1633
PAQR3 has modulatory roles in obesity, energy metabolism and leptin signaling
Lingdi Wang, Xiao Wang, Zhenghu Li, Tingting Xia, Lu Zhu, Bing Liu, Yongxian Zhang, Fei Xiao, Yi Pan, Yong Liu, Feifan Guo and Yan Chen
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 revered by Paqr3 ablation. Overexpression of PAQR3 reduces leptin signaling while down-regulation 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.
