小柯机器人

美国德克萨斯大学西南医学中心Bruce Beutler和Zhao Zhang共同合作近期取得重要工作进展，他们通过研究OVOL2突变引起的肥胖揭示了OVOL2在促进产热和限制白色脂肪生成方面的双重作用。相关论文2022年10月12日在线出版于《细胞—代谢》杂志上。

利用小鼠的随机种系突变，研究人员发现了转录因子编码基因Ovol2的一个亚效等位基因（boh），该基因导致肥胖，肥胖最初与正常的食物摄入和身体活动有关，但能量消耗减少。在12周大的boh同型小鼠中，脂肪重量急剧增加，而瘦肉重量减少，到24周时，最终导致大量肥胖、肝脏萎缩、胰岛素抵抗和糖尿病。Ovol2^boh/boh基因型增加了Lep^ob/ob小鼠的肥胖，配对喂养未能使Ovol2^boh/boh小鼠的肥胖正常化。OVOL2缺陷小鼠极不耐冷。

OVOL2是棕色/米色脂肪组织介导的产热所必需的。在白色脂肪组织中，OVOL2通过阻断C/EBPα与其转录靶标的结合来限制脂肪形成。在高脂肪饮食喂养的小鼠脂肪细胞中过量表达OVOL2，可以减少身体和肝脏的总脂肪，改善胰岛素敏感性。他们的数据显示，OVOL2在产热和脂肪生成中发挥双重功能，以维持能量平衡。

附：英文原文

Title: Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis

Author: Zhao Zhang, Yiao Jiang, Lijing Su, Sara Ludwig, Xuechun Zhang, Miao Tang, Xiaohong Li, Priscilla Anderton, Xiaoming Zhan, Mihwa Choi, Jamie Russell, Chun-Hui Bu, Stephen Lyon, Darui Xu, Sara Hildebrand, Lindsay Scott, Jiexia Quan, Rochelle Simpson, Qihua Sun, Baifang Qin, Tiffany Collie, Meron Tadesse, Eva Marie Y. Moresco, Bruce Beutler

Issue&Volume: 2022-10-12

Abstract: Using random germline mutagenesis in mice, we identified a viable hypomorphic allele(boh) of the transcription-factor-encoding gene Ovol2 that resulted in obesity, which initially developed with normal food intake and physicalactivity but decreased energy expenditure. Fat weight was dramatically increased,while lean weight was reduced in 12-week-old boh homozygous mice, culminating by 24 weeks in massive obesity, hepatosteatosis, insulinresistance, and diabetes. The Ovol2boh/boh genotype augmented obesity in Lepob/ob mice, and pair-feeding failed to normalize obesity in Ovol2boh/boh mice. OVOL2-deficient mice were extremely cold intolerant. OVOL2 is essential forbrown/beige adipose tissue-mediated thermogenesis. In white adipose tissues, OVOL2limited adipogenesis by blocking C/EBPα engagement of its transcriptional targets.Overexpression of OVOL2 in adipocytes of mice fed with a high-fat diet reduced totalbody and liver fat and improved insulin sensitivity. Our data reveal that OVOL2 playsdual functions in thermogenesis and adipogenesis to maintain energy balance.

DOI: 10.1016/j.cmet.2022.09.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00408-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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