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脂肪命运的转折:脂滴和炎症性脂质介质。

A twist of FATe: Lipid droplets and inflammatory lipid mediators.

机构信息

Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, SI-1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova cesta 39, Ljubljana, SI-1000, Slovenia.

Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, SI-1000, Slovenia.

出版信息

Biochimie. 2020 Feb;169:69-87. doi: 10.1016/j.biochi.2019.11.016. Epub 2019 Nov 28.

DOI:10.1016/j.biochi.2019.11.016
PMID:31786231
Abstract

Lipid droplets are fat storage organelles present in most eukaryotic cells. They consist of a neutral lipid core containing mostly triglycerides and sterol esters and covered by a monolayer of phospholipids, wherein numerous proteins are embedded. In the cell, lipid droplets have a dynamic life cycle, rapidly altering their size, location, lipid and protein composition in response to environmental stimuli and cell state. Lipid droplets are primarily involved in the coordination of lipid metabolism with cellular requirements for energy production, membrane homeostasis and cell growth. However, they are also directly or indirectly engaged in signalling pathways. On the one hand, lipid droplets sequester lipids and proteins thereby limiting their availability for participation in signalling pathways. On the other hand, the lipolytic machinery provides a highly regulated, on-demand source of signalling lipids: lipids derived from their neutral lipid core, or the phospholipid monolayer, directly act as signalling mediators or are converted into ones. In fact, emerging studies suggest that these organelles are essential for various cellular stress response mechanisms, including inflammation and immunity, acting as hubs that integrate metabolic and inflammatory processes. Here, we discuss the ways in which lipid droplets regulate the availability of fatty acids for the activation of signalling pathways and for the production of polyunsaturated fatty acid-derived lipid mediators. We focus in particular on recent discoveries in immune cells and adipose tissue that have revealed an intricate relationship between lipid droplets and inflammatory signalling and may also be relevant for other tissues and various human diseases.

摘要

脂滴是存在于大多数真核细胞中的脂肪储存细胞器。它们由一个中性脂质核心组成,主要包含甘油三酯和固醇酯,并被一层磷脂覆盖,其中嵌入了许多蛋白质。在细胞中,脂滴具有动态的生命周期,能够快速改变其大小、位置、脂质和蛋白质组成,以响应环境刺激和细胞状态的变化。脂滴主要参与协调脂质代谢与细胞对能量产生、膜稳态和细胞生长的需求。然而,它们也直接或间接地参与信号通路。一方面,脂滴隔离脂质和蛋白质,从而限制它们参与信号通路的可用性。另一方面,脂解机制提供了一种高度调控的、按需的信号脂质来源:来自中性脂质核心或磷脂单层的脂质可直接作为信号介质,或者被转化为信号介质。事实上,新出现的研究表明,这些细胞器对于各种细胞应激反应机制(包括炎症和免疫)是必不可少的,它们作为整合代谢和炎症过程的枢纽发挥作用。在这里,我们讨论了脂滴调节脂肪酸可用性的方式,以激活信号通路和产生多不饱和脂肪酸衍生的脂质介质。我们特别关注在免疫细胞和脂肪组织中最近的发现,这些发现揭示了脂滴与炎症信号之间复杂的关系,这可能也与其他组织和各种人类疾病有关。

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