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外泌体在儿童和青少年肥胖中的潜在作用

The Potential Role of Exosomes in Child and Adolescent Obesity.

作者信息

Maligianni Ioanna, Yapijakis Christos, Bacopoulou Flora, Chrousos George

机构信息

Unit of Orofacial Genetics, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, 1 Thivon Street, Goudi, 11527 Athens, Greece.

University Research Institute of Maternal and Child Health and Precision Medicine, UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, 8 Livadias Street, Goudi, 11527 Athens, Greece.

出版信息

Children (Basel). 2021 Mar 6;8(3):196. doi: 10.3390/children8030196.

Abstract

Child and adolescent obesity constitute one of the greatest contemporary public health menaces. The enduring disproportion between calorie intake and energy consumption, determined by a complex interaction of genetic, epigenetic, and environmental factors, finally leads to the development of overweight and obesity. Child and adolescent overweight/obesity promotes smoldering systemic inflammation ("para-inflammation") and increases the likelihood of later metabolic and cardiovascular complications, including metabolic syndrome and its components, which progressively deteriorate during adulthood. Exosomes are endosome-derived extracellular vesicles that are secreted by a variety of cells, are naturally taken-up by target cells, and may be involved in many physiological and pathological processes. Over the last decade, intensive research has been conducted regarding the special role of exosomes and the non-coding (nc) RNAs they contain (primarily micro (mi) RNAs, long (l) non-coding RNAs, messenger (m) RNAs and other molecules) in inter-cellular communications. Through their action as communication mediators, exosomes may contribute to the pathogenesis of obesity and associated disorders. There is increasing evidence that exosomal miRNAs and lncRNAs are involved in pivotal processes of adipocyte biology and that, possibly, play important roles in gene regulation linked to human obesity. This review aims to improve our understanding of the roles of exosomes and their cargo in the development of obesity and related metabolic and inflammatory disorders. We examined their potential roles in adipose tissue physiology and reviewed the scarce data regarding the altered patterns of circulating miRNAs and lncRNAs observed in obese children and adolescents, compared them to the equivalent, more abundant existing findings of adult studies, and speculated on their proposed mechanisms of action. Exosomal miRNAs and lncRNAs could be applied as cardiometabolic risk biomarkers, useful in the early diagnosis and prevention of obesity. Furthermore, the targeting of crucial circulating exosomal cargo to tissues involved in the pathogenesis and maintenance of obesity could provide a novel therapeutic approach to this devastating and management-resistant pandemic.

摘要

儿童和青少年肥胖是当代最大的公共卫生威胁之一。热量摄入与能量消耗之间长期存在的不均衡,由遗传、表观遗传和环境因素的复杂相互作用所决定,最终导致超重和肥胖的发生。儿童和青少年超重/肥胖会引发隐匿性全身炎症(“副炎症”),并增加日后发生代谢和心血管并发症的可能性,包括代谢综合征及其组分,这些在成年期会逐渐恶化。外泌体是源自内体的细胞外囊泡,由多种细胞分泌,可被靶细胞自然摄取,并可能参与许多生理和病理过程。在过去十年中,针对外泌体及其所含非编码(nc)RNA(主要是微小(mi)RNA、长(l)非编码RNA、信使(m)RNA和其他分子)在细胞间通讯中的特殊作用进行了深入研究。通过作为通讯介质发挥作用,外泌体可能参与肥胖及其相关疾病的发病机制。越来越多的证据表明,外泌体miRNA和lncRNA参与脂肪细胞生物学的关键过程,并且可能在与人类肥胖相关的基因调控中发挥重要作用。本综述旨在增进我们对外泌体及其所载物质在肥胖以及相关代谢和炎症性疾病发展中作用的理解。我们研究了它们在脂肪组织生理学中的潜在作用,回顾了关于肥胖儿童和青少年中循环miRNA和lncRNA改变模式的稀少数据,并将其与成人研究中更丰富的现有等效发现进行比较,同时推测了它们的作用机制。外泌体miRNA和lncRNA可作为心脏代谢风险生物标志物,有助于肥胖的早期诊断和预防。此外,将关键的循环外泌体所载物质靶向到参与肥胖发病机制和维持的组织,可能为这种具有破坏性且难以管理的流行病提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/813e/7999028/2f3e28c178f8/children-08-00196-g001.jpg

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