长久以来,关于脂滴是如何生成、变大的问题一直悬而未决。脂代谢紊乱能够引起多种代谢性疾病如肥胖、糖尿病、脂肪肝、动脉粥样硬化等,严重危害人类健康。脂滴(Lipid Droplet)作为脂代谢的核心细胞器能够特异地储存中性脂,其数目和大小与脂代谢的平衡有着密切关系。
清华大学生命学院教授、清华-北大生命科学联合中心研究员李蓬所领导的研究组首次发现了一种全新的脂滴融合分子机制:CIDE家族蛋白Fsp27通过在脂滴-脂滴接触点富集介导脂肪的转移来诱导脂滴融合长大,并进行了系统深入地研究。
本论文研究发现Fsp27蛋白在脂滴-脂滴接触点,即LDCS(LD contacting site)上大量富集,荧光漂白实验(FRAP)表明在野生型脂肪细胞和Fsp27蛋白过表达的细胞中成对的脂滴间能发生中性脂的转移,而Fsp27缺失的脂肪细胞则不能。活细成像技术(Live image)进一步揭示当两个大小不同的脂滴接触时, Fsp27蛋白介导中性脂经LDCS由小脂滴向大脂滴的定向转移,从而形成一个较大的脂滴。上述研究成果首次提出了一种脂滴生长的全新分子机制:即Fsp27通过在脂滴接触点介导脂滴的生长。为以后研究脂滴的形成、长大奠定了理论基础,并为进一步以脂滴为药物靶点来治疗脂紊乱疾病提供了重要的理论依据。(生物谷Bioon.com)
doi: 10.1083/jcb.201104142
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Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites
Jingyi Gong, Zhiqi Sun1 Lizhen Wu, Wenyi Xu, Nicole Schieber, Dijin Xu, Guanghou Shui, Hongyuan Yang, Robert G. Parton, and Peng Li.
Lipid droplets (LDs) are dynamic cellular organelles that control many biological processes. However, molecular components determining LD growth are poorly understood. Genetic analysis has indicated that Fsp27, an LD-associated protein, is important in controlling LD size and lipid storage in adipocytes. In this paper, we demonstrate that Fsp27 is focally enriched at the LD–LD contacting site (LDCS). Photobleaching revealed the occurrence of lipid exchange between contacted LDs in wild-type adipocytes and Fsp27-overexpressing cells but not Fsp27-deficient adipocytes. Furthermore, live-cell imaging revealed a unique Fsp27-mediated LD growth process involving a directional net lipid transfer from the smaller to larger LDs at LDCSs, which is in accordance with the biophysical analysis of the internal pressure difference between the contacting LD pair. Thus, we have uncovered a novel molecular mechanism of LD growth mediated by Fsp27.