Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in Drosophila showed that body size plasticity was higher in females, yet the mechanisms underlying increased female body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-biased increase in activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS). This sex-biased upregulation of IIS activity was triggered by a diet-induced increase in stunted mRNA in females, and required Drosophila insulin-like peptide 2, illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene transformer promotes the diet-induced increase in stunted mRNA via transcriptional coactivator Spargel to regulate the male-female difference in body size plasticity. Together, these findings provide vital insight into conserved mechanisms underlying the sex difference in nutrient-dependent body size plasticity.

Automated summary

This study found that a protein-rich diet increases body size in female fruit flies, but not males, by enhancing the activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS). The sex-biased upregulation of IIS activity in females is triggered by a diet-induced increase in stunted mRNA, revealing new sex-specific roles for certain genes. Additionally, the sex determination gene transformer promotes the diet-induced increase in stunted mRNA via the transcriptional coactivator Spargel to regulate the difference in body size plasticity between males and females.