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自然选择与人类肥胖:狡猾的基因型,节俭的表型。

Natural selection and human adiposity: crafty genotype, thrifty phenotype.

机构信息

Childhood Nutrition Research Centre, Population Policy and Practice Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2023 Sep 11;378(1885):20220224. doi: 10.1098/rstb.2022.0224. Epub 2023 Jul 24.

Abstract

Evolutionary perspectives on obesity have aimed to understand how the genetic constitution of individuals has been shaped by selective pressures such as famine, predation or infectious disease. The dual intervention model assumes strong selection on lower and upper limits of adiposity, but negligible fitness implications for intermediate adiposity. These frameworks are agnostic to age, sex and condition. I argue that selection has favoured a 'crafty genotype'-a genetic basis for accommodating variability in the 'fitness value' of fat through phenotypic plasticity, depending on the endogenous and exogenous characteristics of each individual. Hominin evolution occurred in volatile environments. I argue that the polygenetic basis of adiposity stabilizes phenotype in such environments, while also coordinating phenotypic variance across traits. This stability underpins reaction norms through which adiposity can respond sensitively to ecological factors. I consider how the fitness value of fat changes with age, sex and developmental experience. Fat is also differentially distributed between peripheral and abdominal depots, reflecting variable prioritization of survival versus reproduction. Where longevity has been compromised by undernutrition, abdominal fat may promote immediate survival and fitness, while long-term cardiometabolic risks may never materialize. This approach helps understand the sensitivity of adiposity to diverse environmental factors, and why the health impacts of obesity are variable. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

摘要

肥胖的进化观点旨在理解个体的遗传构成是如何受到选择压力的影响而形成的,如饥荒、捕食或传染病。双重干预模型假设对脂肪的下限和上限有很强的选择,但对中间脂肪的适应性影响可以忽略不计。这些框架对年龄、性别和条件是不可知的。我认为,选择有利于一种“狡猾的基因型”,即通过表型可塑性来适应脂肪“适应值”的可变性的遗传基础,这取决于每个人的内源性和外源性特征。人类进化发生在不稳定的环境中。我认为,肥胖的多基因基础在这种环境中稳定了表型,同时协调了不同性状之间的表型变异。这种稳定性为反应规范提供了基础,使脂肪能够对生态因素做出敏感的反应。我考虑了脂肪的适应值如何随年龄、性别和发育经验而变化。脂肪在身体外周和腹部之间的分布也存在差异,反映了生存与繁殖之间的可变优先排序。在营养不足导致长寿受到损害的情况下,腹部脂肪可能会促进即时的生存和适应性,而长期的心血管代谢风险可能永远不会出现。这种方法有助于理解脂肪对各种环境因素的敏感性,以及为什么肥胖对健康的影响是多变的。本文是“肥胖成因:理论、推测和证据(第一部分)”讨论会议的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd0/10363707/7fc291d8b17d/rstb20220224f01.jpg

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