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

Abstract

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in <i>Drosophila</i> 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 <i>stunted</i> mRNA in females, and required <i>Drosophila insulin-like peptide 2</i>, illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene <i>transformer</i> promotes the diet-induced increase in <i>stunted</i> 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.