Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8208, St. Louis, MO 63110, USA.
Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8208, St. Louis, MO 63110, USA.
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1255-1263. doi: 10.1016/j.bbadis.2017.03.014. Epub 2017 Mar 24.
As the obesity epidemic worsens, the prevalence of maternal obesity is expected to rise. Both high-fat and high-sucrose diets are known to promote maternal obesity and several studies have elucidated the molecular influence of high-fat feeding on female reproduction. However, to date, the molecular impact of a high-sucrose diet on maternal obesity remains to be investigated. Using our previously reported Drosophila high-sucrose maternal obesity model, we sought to determine how excess dietary sucrose impacted the ovary. High-sucrose diet (HSD) fed adult females developed systemic insulin resistance and exhibited an ovarian phenotype characterized by excess accumulation of lipids and cholesterol in the ovary, decreased ovary size, and impaired egg maturation. We also observed decreased expression of antioxidant genes and increased protein carbonylation in the ovaries of HSD females. HSD females laid fewer eggs; however, the overall survival of offspring was unchanged relative to lean control females. Ovaries of HSD females had increased mitochondrial DNA copy number and decreased expression of key mitochondrial regulators, suggestive of an ineffective compensatory response to mitochondrial dysfunction. Mitochondrial alterations were also observed in male offspring of obese females. This study demonstrates that high-sucrose-induced maternal obesity promotes insulin resistance, while disrupting ovarian metabolism and function.
随着肥胖症的流行加剧，预计母体肥胖的患病率将会上升。众所周知，高脂肪和高糖饮食都会导致母体肥胖，并且有几项研究已经阐明了高脂肪喂养对女性生殖的分子影响。然而，迄今为止，高糖饮食对母体肥胖的分子影响仍有待研究。使用我们之前报道的果蝇高糖母体肥胖模型，我们试图确定过量的饮食蔗糖如何影响卵巢。高糖饮食（HSD）喂养的成年雌性果蝇会发展出系统性胰岛素抵抗，并表现出卵巢表型，其特征是卵巢中脂质和胆固醇过度积累、卵巢体积减小以及卵成熟受损。我们还观察到 HSD 雌性果蝇的抗氧化基因表达降低和蛋白质羰基化增加。HSD 雌性产卵较少；然而，与瘦对照组雌性相比，后代的整体存活率没有变化。HSD 雌性的卵巢线粒体 DNA 拷贝数增加，关键线粒体调节剂的表达降低，提示线粒体功能障碍的无效代偿反应。肥胖雌性雄性后代也观察到线粒体改变。这项研究表明，高糖诱导的母体肥胖会促进胰岛素抵抗，同时破坏卵巢代谢和功能。
