Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling inDrosophilalarvae

Abstract

SUMMARYThe fat body inDrosophilalarvae serves as a reserve tissue and participates, through its endocrine function, in the regulation of organismal growth and homeostasis. To better understand its role in growth coordination, we induced severe fat body atrophy by knocking down in adipose cells several key enzymes of the glycolytic pathway. Our results show that impairing the last steps of glycolysis led to a drastic shrinkage in adipose cell size and lipid droplets content, and a downregulation of the mTOR pathway. Strikingly, fat body atrophy resulted in the distant disorganization of body wall muscles and the release of muscle-specific proteins in the hemolymph. Molecularly we showed that REPTOR activity was required for fat body atrophy downstream of glycolysis inhibition, and that the effect of fat body atrophy on muscles did not require upd3 secretion, but depended the production of egr/TNF-α and of the insulin pathway inhibitor ImpL2.