A low-sugar diet enhances Drosophila body size in males and females via sex-specific mechanisms

In Drosophila, changes to dietary protein elicit different body size responses between the sexes. Whether these differential body size effects extend to other macronutrients remains unclear. Here, we show that lowering dietary sugar (0S diet) enhanced body size in male and female larvae. Despite an equivalent phenotypic effect between the sexes, we detected sex-specific changes to signalling pathways, transcription and whole-body glycogen and protein. In males, the low-sugar diet augmented insulin/insulin-like growth factor signalling pathway (IIS) activity by increasing insulin sensitivity, where increased IIS was required for male metabolic and body size responses in 0S. In females reared on low sugar, IIS activity and insulin sensitivity were unaffected, and IIS function did not fully account for metabolic and body size responses. Instead, we identified a female-biased requirement for the Target of rapamycin pathway in regulating metabolic and body size responses. Together, our data suggest the mechanisms underlying the low-sugar-induced increase in body size are not fully shared between the sexes, highlighting the importance of including males and females in larval studies even when similar phenotypic outcomes are observed.

Automated summary

Changes in dietary protein in Drosophila have different effects on body size between males and females. This study found that reducing dietary sugar can increase body size in male and female larvae, but there are sex-specific changes in signaling pathways, transcription, and whole-body glycogen and protein. In males, the low-sugar diet enhances insulin/insulin-like growth factor signaling pathway activity by increasing insulin sensitivity, while females require the Target of rapamycin pathway to regulate metabolic and body size responses.