Saad Mario J A, Santos Andrey
Department of Internal Medicine, School of Medical Sciences, University of Campinas, CEP 13083-887 Campinas, SP, Brazil.
Endocr Rev. 2025 Mar 11;46(2):300-316. doi: 10.1210/endrev/bnae033.
Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by environmental pathogens, specific genes that help develop a robust defense mechanism against infectious diseases have had evolutionary advantages and that this may contribute to obesity in modern times due to connections between the immune and energy storage systems. Indeed, incorporating the genetic variations of gut microbiota into the complex genetic framework of obesity makes it more polygenic than previously believed. Thus, uncovering the evolutionary origins of obesity requires a multifaceted approach that considers the complexity of human history, the unique genetic makeup of different populations, and the influence of gut microbiome on host genetics.
肥胖是一个主要的全球问题,通常归因于遗传和环境因素的综合作用。已经提出了几种假说来解释肥胖流行的进化起源,包括节俭和漂移基因型以及产热变化。在这里,我们提出了元炎症假说,该假说认为,由于环境病原体施加的强烈选择压力,有助于建立强大的抗感染防御机制的特定基因具有进化优势,并且由于免疫和能量储存系统之间的联系,这可能在现代导致肥胖。事实上,将肠道微生物群的遗传变异纳入肥胖的复杂遗传框架中,使其比以前认为的更具多基因性。因此,揭示肥胖的进化起源需要一种多方面的方法,该方法要考虑人类历史的复杂性、不同人群独特的基因构成以及肠道微生物群对宿主遗传学的影响。