A high-sugar diet (HSD) can cause obesity and insulin resistance, while also reducing fertility and stem cell function. However, decoupling whether HSD-induced metabolic responses or obesity-related disease causes these effects has been challenging. In Development’s Special Issue: Metabolic and Nutritional Control of Development and Regeneration, Daniela Drummond-Barbosa and Rodrigo Dutra Nunes determine that a HSD, but not obesity, reduces female fertility in Drosophila. The authors show that HSD-induced obesity increases the death of early germline cysts and causes egg chamber degeneration without affecting germline stem cell (GSC) proliferation or egg chamber growth. However, genetic models of obesity (such as Brummer knockdown flies) have normal fertility, demonstrating HSD-specific effects. A HSD increases sugar levels and insulin resistance in the fat body, which are not observed in genetically obese females. Interestingly, hydration restores fertility and normal glucose levels in HSD-obese females. In this issue, Hweijan Hsu, Chau-Ti Ting and colleagues show that a 1-week HSD induces obesity and attenuates lipid metabolism in the ovary and intestine, independently of insulin resistance. They reveal that a HSD affects GSC proliferation, which is a discrepancy between the two studies. The HSD also affects intestinal stem cell maintenance and differentiation via increased JNK signalling, which is induced by reactive oxygen species. Tumorous stem cells, however, do not respond to the HSD – potentially because of different metabolic requirements. Together, these studies suggest obesity-independent causality between a HSD, reduced fecundity and disruption of stem cell lineages.
