Modeling Obesity-Associated Ovarian Dysfunction in Drosophila.
Modeling Obesity-Associated Ovarian Dysfunction in Drosophila.
复制标题
果蝇肥胖相关卵巢功能障碍的建模
作者：
我们进行定量研究，以探讨高热量饮食对果蝇卵子发生的影响。我们使用中心复合设计（CCD）的方法，获得二次回归模型的体脂和生育能力的蛋白质和蔗糖，在果蝇饮食中的两个主要的常量营养素的浓度的函数，和治疗持续时间。我们的研究结果揭示了蔗糖和蛋白质之间复杂的相互作用，当它们被认为是一个综合的生理反应时，它们会影响体脂和生育能力。我们验证我们的定量建模方法的实用性，通过实验确认的生理反应，包括增加体脂肪，降低生育能力，卵巢胰岛素不敏感性，预期的治疗条件，确定我们的建模方法。在这种治疗条件下，我们发现了一种果蝇卵子发生表型，其表现出未成熟卵母细胞的积累和成熟卵母细胞生产的停止，这种表型与人类多囊卵巢综合征（PCOS）的关键方面相似。我们对饮食诱导的病理生理学不同方面的动态进展的分析也表明了肥胖、卵巢功能障碍和胰岛素抵抗的发病时间顺序。因此，我们的研究记录了定量建模方法的效用，以了解果蝇雌性生殖的生物学，与饮食诱导的肥胖和II型糖尿病有关，作为人类卵巢功能障碍的潜在疾病模型。
We perform quantitative studies to investigate the effect of high-calorie diet on Drosophila oogenesis. We use the central composite design (CCD) method to obtain quadratic regression models of body fat and fertility as a function of the concentrations of protein and sucrose, two major macronutrients in Drosophila diet, and treatment duration. Our results reveal complex interactions between sucrose and protein in impacting body fat and fertility when they are considered as an integrated physiological response. We verify the utility of our quantitative modeling approach by experimentally confirming the physiological responses—including increased body fat, reduced fertility, and ovarian insulin insensitivity—expected of a treatment condition identified by our modeling method. Under this treatment condition, we uncover a Drosophila oogenesis phenotype that exhibits an accumulation of immature oocytes and a halt in the production of mature oocytes, a phenotype that bears resemblance to key aspects of the human condition of polycystic ovary syndrome (PCOS). Our analysis of the dynamic progression of different aspects of diet-induced pathophysiology also suggests an order of the onset timing for obesity, ovarian dysfunction, and insulin resistance. Thus, our study documents the utility of quantitative modeling approaches toward understanding the biology of Drosophila female reproduction, in relation to diet-induced obesity and type II diabetes, serving as a potential disease model for human ovarian dysfunction.