山东大学孙金鹏小组取得一项新突破。他们的研究开发出了Or5v1/Olfr110作为氧化脂素受体和抗肥胖靶点的鉴定。相关论文于2026年1月21日发表于国际顶尖学术期刊《细胞》杂志上。
通过建立“反向g蛋白拉下匿名受体鉴定”（ARIG）方法，该课题组研究人员鉴定孤儿OR Or5v1/Olfr110为氧脂素12(S)-羟二碳五烯酸（12(S)-HEPE）受体。BMI升高的肥胖患者血清Or5v1/Olfr110-Gs活性低于正常人。系统性Or5v1/Olfr110缺乏或肝脏特异性Or5v1/Olfr110缺乏会损害葡萄糖稳态，即使在12(S)-HEPE刺激后也是如此。12(S)-HEPE与Olfr110结合激活Gs-PKA-pATF2-Cpt1α信号，通过促进肝脏脂肪酸氧化来减少肥胖。合成激动剂HOR1-C59的结构辅助开发改善了葡萄糖稳态，这依赖于Or5v1/Olfr110的表达。总之，研究团队发现一个高亲和力的氧脂感应OR在代谢中起关键作用。HOR1-C59的有益作用强调了靶向ORs的小合成化合物在疾病治疗中的治疗价值。
据悉，氧化脂素是正常生命活动的重要代谢信使，而嗅觉受体（ORs）因其对气味的亲和力较低而不被认为是氧化脂素受体。
附：英文原文
Title: Identification of Or5v1/Olfr110 as an oxylipin receptor and anti-obesity target
Author: Xiao-Yan Ge, Jie Cheng, Li-Jun Zhang, Lu-Lu Guo, Rui Xiang, Yan Lu, Shang-Lei Ning, Kai-Yu Wang, Kong-Kai Zhu, Ming-Xin Gao, Yue Li, Yu-Song Zhang, Nai-Kang Rong, Xiang Han, Ming-Hui Zhang, Le Fang, Yun-Fei Xu, Su-Wen Zhao, Qian Li, Fan Yang, Yong Hao, Ren-Jie Chai, Xiao Yu, Ji-Chun Yang, Jin-Peng Sun
Issue&Volume: 2026-01-21
Abstract: Oxylipins are important metabolic messengers for normal life activities, and olfactory receptors (ORs) are known for their low affinity for odor and are not considered oxylipin receptors. By developing the “anonymous receptor identification by reverse-G-protein pull-down” (ARIG) method, we identify orphan OR Or5v1/Olfr110 as an oxylipin 12(S)-hydroxyeicosapentaenoic acid (12(S)-HEPE) receptor. The serum from obese patients with increased BMI showed lower Or5v1/Olfr110-Gs activation compared with normal people. Systemic Or5v1/Olfr110 deficiency or liver-specific Or5v1/Olfr110 deficiency impaired glucose homeostasis, even after stimulation with 12(S)-HEPE. Engagement of 12(S)-HEPE with Olfr110 activated Gs-PKA-pATF2-Cpt1α signaling to reduce obesity through promotion of fatty acid oxidation in liver. Structural aided development of synthetic agonist HOR1-C59 improved glucose homeostasis, which is dependent on Or5v1/Olfr110 expression. Overall, we revealed that a high-affinity oxylipin-sensing OR plays key roles in metabolism. The beneficial effects of HOR1-C59 underscore the therapeutic value of small synthetic compounds that target ORs for disease treatment.
DOI: 10.1016/j.cell.2025.12.016
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01429-1