The AMPK-PP2A axis in insect fat body is activated by 20-hydroxyecdysone to antagonize insulin/IGF signaling and restrict growth rate

Significance Final body size determination in animals remains a long-standing puzzle in the field of developmental biology. In insects, insulin/insulin-like growth factor signaling (IIS) and the steroid hormone 20-hydroxyecdysone (20E) are mainly responsible for the growth rate and growth period, respectively, and consequently the final body size. Here, we report that 20E activates AMPK by up-regulating its gene expression and inducing sugar starvation. In turn, AMPK activates protein phosphatase 2A, which further dephosphorylates and inactivates key components in IIS in the fat body, and eventually suppresses the larval growth rate. These data answer the question of how 20E antagonizes IIS and modulates growth rate.