小柯机器人

北京大学医学部Yuxin Yin和Yongfeng Song共同合作近期取得重要工作进展，他们研究发现去泛素酶OTUD3能够调节应对营养应激的代谢稳态。该项研究成果2022年6月7日在线发表于《细胞—代谢》杂志上。

研究人员在一个糖尿病发病年龄较早的家庭中发现了一种罕见的OTUD3 c.863G>A突变。这种突变降低了OTUD3的稳定性和催化活性。接下来，研究人员用Otud3^-/-小鼠构建了一个实验，发现当受到高脂饮食 (HFD) 的挑战时，它们比野生型小鼠更易出现更严重的肥胖、血脂异常和胰岛素抵抗。他们进一步发现葡萄糖和脂肪酸刺激CREB结合蛋白依赖性OTUD3乙酰化，促进其核转位，其中OTUD3通过稳定过氧化物酶体增殖物激活受体delta (PPARδ) 参与调节与葡萄糖、脂质代谢和氧化磷酸化的各种基因。

此外，使用特定激动剂靶向PPARδ可以部分挽救HFD喂养的Otud3^-/-小鼠的表型。研究人员提出OTUD3是能量代谢的重要调节因子，并且OTUD3 c.863G>A与肥胖和更高的糖尿病风险有关。

据介绍，含有卵巢肿瘤结构域的去泛素酶(OTUDs)阻断泛素依赖的蛋白降解，并参与多种信号通路。

附：英文原文

Title: Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses

Author: Na Zhou, Hailong Qi, Junjun Liu, Guangze Zhang, Jianping Liu, Ning Liu, Minglu Zhu, Xuyang Zhao, Chang Song, Zhe Zhou, Jingjing Gong, Ridong Li, Xinyu Bai, Yan Jin, Yongfeng Song, Yuxin Yin

Issue&Volume: 2022-06-07

Abstract: The ovarian-tumor-domain-containing deubiquitinases (OTUDs) block ubiquitin-dependentprotein degradation and are involved in diverse signaling pathways. We discovereda rare OTUD3 c.863G>A mutation in a family with an early age of onset of diabetes. This mutation reducesthe stability and catalytic activity of OTUD3. We next constructed an experiment withOtud3/ mice and found that they developed worse obesity, dyslipidemia, and insulin resistancethan wild-type mice when challenged with a high-fat diet (HFD). We further found thatglucose and fatty acids stimulate CREB-binding-protein-dependent OTUD3 acetylation,promoting its nuclear translocation, where OTUD3 regulates various genes involvedin glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activatedreceptor delta (PPARδ). Moreover, targeting PPARδ using a specific agonist can partiallyrescue the phenotype of HFD-fed Otud3/ mice. We propose that OTUD3 is an important regulator of energy metabolism and thatthe OTUD3 c.863G>A is associated with obesity and a higher risk of diabetes.

DOI: 10.1016/j.cmet.2022.05.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00187-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx