The Drosophila Estrogen-Related Receptor acts within the larval fat body to promote triglyceride storage
Members of the Estrogen-Related Receptor (ERR) family of nuclear receptors (NR) serve a key role in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, loss of ERR activity disrupts (TAG) storage during the post-embryonic growth phase, with loss-of-function mutations in mouseErraandDrosophila melanogaster dERRinducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation remains poorly understood, as previous multiomic studies largely relied on whole animal analyses. Here we address this shortcoming by using tissue-specific approaches to determine how dERR regulates lipid metabolism within theDrosophilalarval fat body. We found that dERR autonomously promotes TAG accumulation within fat body cells by regulating expression of genes involved in glycolysis, the pentose phosphate pathway, lipid synthesis, andb-oxidation. As an extension of these results, we not only discovered thatdERRmutant fat bodies exhibit decreased expression of known HNF4 target genes but also found that dHNF4 activity is decreased indERRmutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with developmental growth and hint at a conserved mechanism by which ERR and HNF4 homologs coordinately regulate metabolic gene expression Overall design: RNA was isolated from both the fat body and whole animal homogenates of mid-L2 ERR[1/2] mutants and ERR[1/+] heterozygous controls