Dumesic Daniel A, Abbott David H, Chazenbalk Gregorio D
Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, WI 53715, USA.
J Clin Med. 2023 Sep 22;12(19):6120. doi: 10.3390/jcm12196120.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today's contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today's obesogenic environment.
多囊卵巢综合征（PCOS）是育龄女性常见的一种内分泌疾病，其特征为雄激素过多、排卵稀少或无排卵以及胰岛素抵抗，且与腹部脂肪优先堆积密切相关。作为灵长类动物的一种原始特征，在更新世晚期狩猎采集者食物匮乏时，为满足后期生殖的代谢需求，人类可能进一步选择了PCOS，以增强脂肪储存。作为PCOS的一种进化模型，患有高雄激素性PCOS的健康正常体重女性具有皮下（SC）腹部脂肪干细胞，这些干细胞在体外发育过程中通过过度积累脂质而有利于脂肪储存，进而形成脂肪细胞。反过来，脂肪储存会因胰岛素敏感性降低和体内高分解代谢的腹部脂肪优先堆积而得到平衡。PCOS中的这种代谢适应将能量储存与葡萄糖可用性以及脂肪酸氧化相平衡，以便在生殖过程中实现最佳能量利用；其伴随的排卵稀少或无排卵使古代的PCOS女性有足够的时间和体力抚养数量较少但童年存活可能性更大的后代。可遗传的PCOS特征在当今的现代环境中会受到表观遗传事件的影响，这些事件使女性易患脂毒性，导致体重过度增加和妊娠并发症，这就要求在当今的致胖环境中强调预防性医疗保健，以优化PCOS女性的长期内分泌代谢健康。
