脂肪组织外泌体的功能和作用机制

The Function and Mechanism of Exosomes Derived from Adipose Tissue

脂肪组织是人体内重要的能量代谢器官,通过储存和消耗能量,进而维持机体的产热和代谢稳态。同时,脂肪组织还可以作为一种分泌器官,分泌一系列脂肪因子:例如瘦蛋白和脂联素等,作用到自身组织和其他代谢组织器官中发挥功能。除了分泌脂肪因子,越来越多的研究集中于脂肪组织向细胞外分泌的囊泡,即外泌体,通过自分泌、旁分泌、内分泌的方式作用到全身组织器官中,维持细胞、组织间的信息交流。在这一过程中,非编码RNA微小核糖核酸(microRNA,miRNA)、环状RNA(circular RNA,circRNA)、长非编码RNA(long non-coding RNA,lncRNA)、蛋白质、脂质等能被外泌体包裹,通过外泌体的形式在机体内循环运输到达靶细胞,调节靶细胞中目的基因转录和蛋白质修饰等,进而影响人体的生理和病理过程。最近的研究表明,棕色脂肪组织能分泌大量外泌体miRNA,通过内分泌的方式运输到肝,调控肝的脂质代谢;白色脂肪组织能通过外泌体miRNA,诱导胰岛素抵抗和肿瘤的发生;血管周围脂肪组织能通过外泌体miRNA,调节血管的重塑。此外,脂肪组织也能通过circRNA、lncRNA以及蛋白质,调控肝组织、肌肉和血管等器官的功能。本文将围绕脂肪组织外泌体中不同内容物在代谢性疾病,例如糖尿病、心血管疾病和肿瘤中发挥的作用进行总结。同时,对外泌体中主要内容物非编码RNA的作用机制进行深入的探讨,以期深入了解脂肪组织外泌体在机体生命活动中不可或缺的作用。

Adipose tissue is an important energy metabolism organ in human body,which maintains heat production and metabolic homeostasis by storing and consuming energy.Meanwhile,it can also act as a secretion organ,secreting a series of adipokines,such as leptin and adiponectin,which plays a role in its own tissues and other metabolic organs.In addition to the secretion of adipokines,more and more studies have focused on the vesicles secreted by adipose tissue,that is,exosomes,which act on tissues and organs throughout the body through autocrine,paracrine and endocrine ways to maintain the crosstalk between organs.In this process,non-coding RNA—microRNA(miRNA),circular RNA(circRNA),long non-coding RNA(lncRNA),proteins,and lipids,etc,can be wrapped by exosomes and transported to target cells,regulating the transcription of target genes and protein modification,and affecting the physiological and pathological processes of the human body.Recent studies have shown that brown adipose tissue can secrete a large number of exosomal miRNA,which can be transported to the liver by endocrine and regulate lipid metabolism.White adipose tissue can induce insulin resistance and tumor development through exosomal miRNA.Perivascular adipose tissue can regulate vascular remodeling.In addition,adipose tissue can also regulate the functions of liver,muscle,blood vessels and other organs through circRNA,lncRNA and proteins.This review will summarize the role of different cargoes in adipose tissue exosomes in metabolic diseases such as diabetes,cardiovascular disease,and cancer,and further explore the mechanism of non-coding RNA in exosomes,in order to understand the indispensable role of adipose tissue exosomes in our life activities.