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

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in 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 mRNA in females, and required , illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene promotes the diet-induced increase in 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.