High-Fat High-Sugar Diet Induces Polycystic Ovary Syndrome in a Rodent Model

Obesity has been linked with a host of metabolic and reproductive disorders including polycystic ovary syndrome (PCOS). While a distinct link exists between obesity and PCOS, the exact pathogenesis of the disease remains less understood and limited research has explored the impact of diet on the development of PCOS. With the primary symptoms of PCOS including hyperandrogenism, anovulation, and polycystic ovaries, most animal models utilize androgen treatment to effectively induce PCOS. However, these models fail to address the underlying causes of disease symptoms and do not effectively demonstrate the metabolic features of the disease such as hyperinsulinemia. Here, we present a novel rodent model of diet-induced obesity that recapitulates both the metabolic and reproductive phenotypes of human PCOS. In utilizing a high-fat high-sugar (HFHS) diet, we have created a model of PCOS that allows for the study of metabolic parameters and their impact on ovarian follicle development and reproductive health. Animals on the HFHS diet not only demonstrated signs of metabolic impairment, but they also developed polycystic ovaries and experienced irregular estrous cycling marked by an extended period spent in estrus. Though hyperandrogenism was not characteristic of HFHS diet animals as a group, testosterone levels were predictive of a polycystic ovarian morphology. Importantly, PCOS was induced similarly to the disease etiology in humans, allowing this model to offer the unique opportunity to study PCOS at its genesis rather than following the development of disease symptoms.肥胖与一系列代谢及生殖系统疾病密切相关，其中就包括多囊卵巢综合征（polycystic ovary syndrome, PCOS）。尽管肥胖与PCOS之间存在明确关联，但该疾病的确切发病机制仍未完全阐明，且目前针对饮食对PCOS发生发展影响的研究较为匮乏。鉴于PCOS的主要症状包括高雄激素血症（hyperandrogenism）、无排卵（anovulation）及多囊卵巢，当前多数动物模型均采用雄激素造模法以高效诱导PCOS。然而，此类模型无法揭示疾病症状的潜在病因，也不能有效呈现该疾病的代谢特征，如高胰岛素血症（hyperinsulinemia）。本研究构建了一种新型饮食诱导肥胖的啮齿类动物模型，该模型可重现人类PCOS的代谢与生殖表型（phenotype）。通过采用高脂高糖（high-fat high-sugar, HFHS）饮食干预，我们成功构建了PCOS模型，可用于研究代谢参数及其对卵巢卵泡发育与生殖健康的影响。饲喂HFHS饮食的动物不仅出现了代谢损伤的相关体征，还形成了多囊卵巢，且动情周期（estrous cycle）出现紊乱，表现为动情期（estrus）时长延长。尽管整体而言，HFHS饮食组动物并未表现出高雄激素血症特征，但睾酮水平可作为多囊卵巢形态的预测指标。尤为重要的是，该模型的PCOS造模过程与人类疾病的病因学（etiology）过程高度契合，使其得以提供独特的研究契机：可在PCOS发生初期而非症状出现后开展相关研究。