Office of Energetics, Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham.
Mayo Clin Proc. 2015 Jan;90(1):77-92. doi: 10.1016/j.mayocp.2014.08.006. Epub 2014 Nov 17.
Over the past century, socioenvironmental evolution (eg, reduced pathogenic load, decreased physical activity, and improved nutrition) led to cumulative increments in maternal energy resources (ie, body mass and adiposity) and decrements in energy expenditure and metabolic control. These decrements reduced the competition between maternal and fetal energy demands and increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother-conceptus energy partitioning stimulated fetal pancreatic β-cell and adipocyte hyperplasia, thereby inducing an enduring competitive dominance of adipocytes over other tissues in the acquisition and sequestering of nutrient energy via intensified insulin secretion and hyperplastic adiposity. At menarche, the competitive dominance of adipocytes was further amplified via hormone-induced adipocyte hyperplasia and weight-induced decrements in physical activity. These metabolic and behavioral effects were propagated progressively when obese, inactive, metabolically compromised women produced progressively larger, more inactive, metabolically compromised children. Consequently, the evolution of human energy metabolism was markedly altered. This phenotypic evolution was exacerbated by increments in the use of cesarean sections, which allowed both the larger fetuses and the metabolically compromised mothers who produced them to survive and reproduce. Thus, natural selection was iatrogenically rendered artificial selection, and the frequency of obese, inactive, metabolically compromised phenotypes increased in the global population. By the late 20th century, a metabolic tipping point was reached at which the postprandial insulin response was so intense, the relative number of adipocytes so large, and inactivity so pervasive that the competitive dominance of adipocytes in the sequestering of nutrient energy was inevitable and obesity was unavoidable.
在过去的一个世纪里,社会环境的演变(例如,致病负荷减少、体力活动减少和营养改善)导致母体能量资源(即体重和肥胖)的累积增加,而能量消耗和代谢控制则减少。这些减少降低了母婴能量需求之间的竞争,并增加了宫内环境中能量底物的可用性。这种母亲-胎儿能量分配的干扰刺激了胎儿胰腺β细胞和脂肪细胞的增生,从而通过加强胰岛素分泌和增生性肥胖,导致脂肪细胞在获取和隔离营养能量方面相对于其他组织的持久竞争优势。在初潮时,通过激素诱导的脂肪细胞增生和体重引起的体力活动减少,脂肪细胞的竞争优势进一步放大。当肥胖、不活跃、代谢受损的女性生育出越来越大、不活跃、代谢受损的孩子时,这些代谢和行为影响会逐渐加剧。因此,人类能量代谢的进化明显改变了。这种表型进化因剖宫产术的增加而加剧,剖宫产术不仅使较大的胎儿,而且使代谢受损的母亲得以存活和繁殖。因此,自然选择被人为选择所取代,肥胖、不活跃、代谢受损的表型在全球人口中的频率增加。到 20 世纪后期,达到了一个代谢转折点,此时餐后胰岛素反应非常强烈,脂肪细胞的相对数量非常大,而且不活跃非常普遍,以至于脂肪细胞在隔离营养能量方面的竞争优势是不可避免的,肥胖也是不可避免的。