Microbiota-dependent inflammation promotes metabolic disorder via NF-κB-mediated inhibition of SREBP inDrosophilaadipocytes

Bacteria that colonize eukaryotic gut have profound influences on the physiology of their host. In Drosophila , many of these effects are mediated by the adipocytes that combine immune and metabolic functions. We show here that gut colonization by specific bacteria species stimulate lipogenesis in surrounding enterocytes but also in remote fat body cells and ovaries. This bacteria-dependent lipid production is mediated by SREBP and requires a functional insulin signaling. However, it is antagonized by microbiota-born peptidoglycan which by activating NF-κB signaling, cell-autonomously represses SREPP activation in adipocytes but not in enterocytes. We finally show that by reducing microbiota-derived PGN, the gut-produced PGRP-LB amidase balances host immune and metabolic responses of the fat body to gut-associated bacteria. In the absence of such modulation, uncontrolled immune pathway activation prevents lipid production by the fat body resulting in infection-dependent host death. Bullets Gut microbiota activates lipogenesis locally in enterocytes and remotely in adipocytes Bacteria-dependent activation of SREBP in adipocytes is mediated by insulin signaling Activation of lipid synthesis by microbiota is antagonized by NF-κB signaling triggered by gut-born peptidoglycan By reducing peptidoglycan circulating levels, PGRP-LB maintains a balance between immune and metabolic response to microbiota