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生命历程中母体代谢外显子组对体重和肥胖的编程作用:系统评价。

Programming of weight and obesity across the lifecourse by the maternal metabolic exposome: A systematic review.

机构信息

Department of Health Sciences, Carleton University, Ottawa, ON, Canada.

Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, AB, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.

出版信息

Mol Aspects Med. 2022 Oct;87:100986. doi: 10.1016/j.mam.2021.100986. Epub 2021 Jun 21.

Abstract

Exposome research aims to comprehensively understand the multiple environmental exposures that influence human health. To date, much of exposome science has focused on environmental chemical exposures and does not take a lifecourse approach. The rising prevalence of obesity, and the limited success in its prevention points to the need for a better understanding of the diverse exposures that associate with, or protect against, this condition, and the mechanisms driving its pathogenesis. The objectives of this review were to 1. evaluate the evidence on the maternal metabolic exposome in the programming of offspring growth/obesity and 2. identify and discuss the mechanisms underlying the programming of obesity. A systematic review was conducted following PRISMA guidelines to capture articles that investigated early life metabolic exposures and offspring weight and/or obesity outcomes. Scientific databases were searched using pre-determined indexed search terms, and risk of bias assessments were conducted to determine study quality. A final total of 76 articles were obtained and extracted data from human and animal studies were visualised using GOfER diagrams. Multiple early life exposures, including maternal obesity, diabetes and adverse nutrition, increase the risk of high weight at birth and postnatally, and excess adipose accumulation in human and animal offspring. The main mechanisms through which the metabolic exposome programmes offspring growth and obesity risk include epigenetic modifications, altered placental function, altered composition of the gut microbiome and breast milk, and metabolic inflammation, with downstream effects on development of the central appetite system, adipose tissues and liver. Understanding early life risks and protectors, and the mechanisms through which the exposome modifies health trajectories, is critical for developing and applying early interventions to prevent offspring obesity later in life.

摘要

暴露组研究旨在全面了解影响人类健康的多种环境暴露因素。迄今为止,大部分暴露组科学研究都集中在环境化学暴露上,并没有采用生命历程的方法。肥胖的患病率不断上升,而预防肥胖的效果有限,这表明我们需要更好地了解与肥胖相关或能预防肥胖的各种暴露因素,以及导致肥胖发病的机制。本综述的目的是:1. 评估母体代谢暴露组在后代生长/肥胖发育中的作用的证据;2. 确定和讨论肥胖发生的机制。本研究按照 PRISMA 指南进行了系统综述,以收集研究早期生活代谢暴露与后代体重和/或肥胖结局的文章。使用预先确定的索引搜索词对科学数据库进行了搜索,并进行了偏倚风险评估以确定研究质量。最终共获得 76 篇文章,并从人类和动物研究中提取数据,使用 GOfER 图进行可视化。多种早期生活暴露因素,包括母体肥胖、糖尿病和不良营养,增加了后代出生时和出生后体重过高以及脂肪过度积累的风险。代谢暴露组通过以下主要机制编程后代的生长和肥胖风险:表观遗传修饰、胎盘功能改变、肠道微生物组和母乳组成改变、代谢性炎症,进而对中枢食欲系统、脂肪组织和肝脏的发育产生下游影响。了解生命早期的风险因素和保护因素,以及暴露组改变健康轨迹的机制,对于开发和应用早期干预措施以预防后代日后肥胖症至关重要。

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