中科院上海生科院營養(yǎng)所陳雁研究組在一項研究中,，發(fā)現(xiàn)并闡明了一個能夠調(diào)節(jié)機體肥胖的關鍵分子,。近日,，相關研究論文在線發(fā)表于《內(nèi)分泌學》。
在研究員陳雁的指導下,，博士生王玲娣等深入研究了在細胞內(nèi)高爾基體特異定位蛋白質(zhì)PAQR3的基因缺失對高脂飲食誘導小鼠發(fā)生肥胖,、肝臟脂肪變性和胰島素抵抗等改變的影響。
研究發(fā)現(xiàn),，PAQR3基因缺失的小鼠可以抵抗高脂飲食誘導產(chǎn)生的肥胖和肝臟脂肪變性,，并伴隨胰島素抵抗和胰島素信號傳導的改善,。PAQR3缺失的小鼠的能量消耗和基礎活動也有一定增強，同時,，PAQR3的缺失可以改善高脂飲食誘導的瘦素抵抗,。在下丘腦中，PAQR3過表達能抑制瘦素信號,；反之,，PAQR3降低則促進瘦素信號。因此,，這一研究表明,，PAQR3在肥胖、能量代謝以及瘦素信號的調(diào)控過程中發(fā)揮重要的生理學功能,。
此前,，陳雁研究組圍繞PAQR3開展了一系列的研究工作，曾發(fā)現(xiàn)PAQR3能夠招募一系列關鍵信號分子,，調(diào)控多個關鍵的細胞信號通路,，參與腫瘤的發(fā)生以及胰島素敏感性的調(diào)控。
此外,，由于PAQR3屬于孕酮和脂聯(lián)素受體（PAQR）家族的一員,，與脂聯(lián)素受體有很高的同源性,，因此該團隊曾推測PAQR3可能參與了肥胖以及能量平衡的調(diào)節(jié)過程,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
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.
