A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan

In gonadal tissues, the Piwi-interacting (piRNA) pathway preserves genomic integrity by employing 23-29nt small RNAs complexed with argonaute proteins to suppress parasitic mobile sequences of DNA called transposable elements (TEs). While recent evidence suggests that the piRNA pathway may be present in select somatic cells outside the gonads, the role of a non-gonadal somatic piRNA pathway is not well characterized. Here we report a functional somatic piRNA pathway in the adult Drosophila fat body including the presence of the piRNA effector protein Piwi and canonical 23-29nt long TE-mapping piRNAs. piwi mutants exhibit depletion of fat body piRNAs, increased TE mobilization, increased levels of DNA damage, and reduced lipid stores. These mutants are starvation-sensitive, immunologically compromised, and short-lived, all phenotypes associated with compromised fat body function. These findings demonstrate the presence of a functional non-gonadal somatic piRNA pathway in the adult fat body that impacts normal metabolism and overall organismal health. RNA-seq: 18 samples total, 6 tissues/genotypes (wild-type head, thorax, abdomen, ovary; piwi2/CyO fat body; and piwi2/piwi2 fat body), 3 replicates each. Small RNA-seq: 6 samples total (wild-type, D. simulans, D. yakuba, ovoD1 mutant, piwi2/CyO, and piwi2/piwi2; all fat body).