Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P₃ Production and Akt Activation.

ABSTRACT: In obese adipose tissue, Toll-like receptor signaling in macrophages leads to insulin resistance in adipocytes. Similarly, Toll signaling in the Drosophila larval fat body blocks insulin-dependent growth and nutrient storage. We find that Toll acts cell autonomously to block growth but not PI(3,4,5)P₃ production in fat body cells expressing constitutively active PI3K. Fat body Toll signaling blocks whole-animal growth in rictor mutants lacking TORC2 activity, but not in larvae lacking Pdk1. Phosphorylation of Akt on the Pdk1 site, Thr342, is significantly reduced by Toll signaling, and expression of mutant Akt^T342D rescues cell and animal growth, nutrient storage, and viability in animals with active Toll signaling. Altogether, these data show that innate immune signa

SUBMITTER: Roth SW 

PROVIDER: S-EPMC5866056 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature