Affiliation: Johns Hopkins Bloomberg School of Public Health
Keywords: b. oogenesis; c. nutrition
Obesity is highly correlated with infertility; however, the underlying mechanisms remain largely unknown. Our previous research revealed complex roles of adipocytes in multiple steps of Drosophila oogenesis, and others have shown that a high sugar diet (HSD) causes obesity and reduces egg production. To carefully investigate how obesity affects oogenesis, we increased dietary sugar content from 5% (ND) to 30% (HSD). In accordance with published studies, females on HSD had a 3-fold increase in triacylglycerol content and lipid droplets, a 2.5-fold increase of glycogen content, and a drastic reduction in egg production and quality compared to ND controls. In addition, we found that these obese females ingested 5 times less food and had increased death of early germline cysts and vitellogenic follicles. In these experiments, however, HSD drives obesity, and it is not clear whether changes in oogenesis are due to HSD, obesity, or both. To test how obesity alone impacts oogenesis, we induced adult adipocyte-specific RNAi against the brummer or adipose genes (both of which inhibit excess fat accumulation). Adipocyte-specific brummer knockdown led to a marked increase in triacylglycerol content and adipocyte lipid droplet size, comparable to those observed in HSD-induced obese females. Strikingly, these highly obese females did not show any significant differences in food ingestion, glycogen content, specific steps of oogenesis, rates of egg production, or oocyte quality relative to non-obese control females. We obtained similar results in obese females generated by adipocyte-specific RNAi against adipose. These results indicate that increased fat storage is not sufficient to reduce fertility. It remains unclear, however, if obesity is required for the reduced fertility of HSD-induced obese females: it is possible that either HSD alone or in combination with obesity is responsible for their fertility defects. Our future studies will investigate the underlying mechanistic basis for the oogenesis differences we observe in these different types of obese females.