Sellayah Dyan
School of Biological Sciences, University of Reading, Reading, Berkshire, United Kingdom.
J Endocr Soc. 2018 Dec 18;3(2):372-386. doi: 10.1210/js.2018-00363. eCollection 2019 Feb 1.
Genetic factors are believed to be primarily responsible for obesity; however, an understanding of how genes for obesity have become so prevalent in modern society has proved elusive. Several theories have attempted to explain the genetic basis for obesity, but none of these appear to factor in the interethnic variation in obesity. Emerging evidence is increasingly pointing to a link between reduced basal metabolism and ineffective brown adipose tissue (BAT) thermogenesis. In fact, BAT presence and function are strongly correlated with metabolic rates and directly influence obesity susceptibility. My colleagues and I recently theorized that ancestral exposure to cold necessitated the evolution of enhanced BAT thermogenesis, which, with today's hypercaloric and sedentary lifestyle, becomes advantageous, because thermogenesis is energetically wasteful, raising basal metabolism and burning excess calories. The opposite may be true for the descendants of heat-adapted populations. This review further reconciles global evolutionary climatic exposures with obesity demographics to understand the genetic basis for the obesity pandemic, and new insights from the most recent studies are provided, including those assessing archaic human admixture. Key genetic variants influencing BAT thermogenesis are outlined that have also been linked with climatic exposure to cold and appear to support the theory that evolutionary factors relevant to climate may have shaped the modern obesity pandemic.
遗传因素被认为是导致肥胖的主要原因;然而,要理解肥胖基因在现代社会中为何如此普遍却并非易事。有几种理论试图解释肥胖的遗传基础,但这些理论似乎都没有考虑到不同种族间肥胖情况的差异。新出现的证据越来越多地表明基础代谢降低与棕色脂肪组织(BAT)产热效率低下之间存在联系。事实上,BAT的存在和功能与代谢率密切相关,并直接影响肥胖易感性。我和我的同事最近提出理论,认为祖先长期暴露在寒冷环境中促使BAT产热增强得以进化,而在如今高热量且久坐不动的生活方式下,这变得具有优势,因为产热会消耗能量,从而提高基础代谢并燃烧多余热量。对于适应炎热环境人群的后代来说,情况可能正好相反。这篇综述进一步梳理了全球进化过程中的气候暴露情况与肥胖人口统计学数据,以理解肥胖大流行的遗传基础,并提供了最新研究的新见解,包括那些评估古代人类基因混合情况的研究。文中概述了影响BAT产热的关键基因变异,这些变异也与寒冷气候暴露有关,似乎支持了这样一种理论,即与气候相关的进化因素可能塑造了现代肥胖大流行。