小柯机器人

美国加州大学Peter Tontonoz团队近期取得重要工作进展，他们研究发现，CLSTN3β通过脂肪细胞的多泡性以促进脂质的利用。相关研究成果2022年12月7日在线发表于《自然》杂志上。

据介绍，多泡脂肪细胞是产热脂肪组织的标志，但影响这种细胞表型的因素在很大程度上是未知的。

研究人员发现，仅存在于胎盘哺乳动物中Clstn3基因座的脂肪细胞选择性产物（Clstn3β）通过限制脂滴（LD）膨胀来促进储存的甘油三酯的有效利用。CLSTN3β是一种整合内质网（ER）膜蛋白，通过保守的发夹状结构域定位于ER–LD接触位点。缺乏CLSTN3β的小鼠具有异常的LD形态和棕色脂肪组织基质的改变，尽管肾上腺素能信号没有缺陷，但对冷诱导的低体温更敏感。相反，CLSTN3β的强制表达足以在培养的细胞和脂肪组织中增强多泡LD表型。CLSTN3β与细胞死亡诱导的DFFA样效应蛋白相关，并削弱其在LD之间转移脂质的能力，从而限制LD的融合和扩张。

在功能上，CLSTN3β表达脂肪细胞中LD表面积的增加促进了脂肪分解机制的参与，并促进了脂肪酸氧化。在人类脂肪中，CLSTN3B是多泡脂肪细胞的选择性标记。

总之，这些发现明确了调节LD形态和功能以促进产热脂肪细胞中脂质利用的分子机制。

 附：英文原文

Title: CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization

Author: Qian, Kevin, Tol, Marcus J., Wu, Jin, Uchiyama, Lauren F., Xiao, Xu, Cui, Liujuan, Bedard, Alexander H., Weston, Thomas A., Rajendran, Pradeep S., Vergnes, Laurent, Shimanaka, Yuta, Yin, Yesheng, Jami-Alahmadi, Yasaman, Cohn, Whitaker, Bajar, Bryce T., Lin, Chia-Ho, Jin, Benita, DeNardo, Laura A., Black, Douglas L., Whitelegge, Julian P., Wohlschlegel, James A., Reue, Karen, Shivkumar, Kalyanam, Chen, Feng-Jung, Young, Stephen G., Li, Peng, Tontonoz, Peter

Issue&Volume: 2022-12-07

Abstract: Multilocular adipocytes are a hallmark of thermogenic adipose tissue1,2, but the factors that enforce this cellular phenotype are largely unknown. Here, we show that an adipocyte-selective product of the Clstn3 locus (CLSTN3β) present in only placental mammals facilitates the efficient use of stored triglyceride by limiting lipid droplet (LD) expansion. CLSTN3β is an integral endoplasmic reticulum (ER) membrane protein that localizes to ER–LD contact sites through a conserved hairpin-like domain. Mice lacking CLSTN3β have abnormal LD morphology and altered substrate use in brown adipose tissue, and are more susceptible to cold-induced hypothermia despite having no defect in adrenergic signalling. Conversely, forced expression of CLSTN3β is sufficient to enforce a multilocular LD phenotype in cultured cells and adipose tissue. CLSTN3β associates with cell death-inducing DFFA-like effector proteins and impairs their ability to transfer lipid between LDs, thereby restricting LD fusion and expansion. Functionally, increased LD surface area in CLSTN3β-expressing adipocytes promotes engagement of the lipolytic machinery and facilitates fatty acid oxidation. In human fat, CLSTN3B is a selective marker of multilocular adipocytes. These findings define a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

DOI: 10.1038/s41586-022-05507-1

Source: https://www.nature.com/articles/s41586-022-05507-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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