INS and Hyperglycemia: We found that shorter lifespan, increased fat storage, reduced insulin sensitivity, and hyperglycemia were associated with systemic activation of the Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway, but not of the NF-κB pathway, in Drosophila maintained under a lipid-rich diet, while Drosophila macrophages became foamy and produced the type 1 cytokine unpaired3 (upd3), which activates the JAK-STAT pathway.