Obesity and obesity-related diseases have become global health issues, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention. By contrast, using C. elegans as a simple model, we identified a conserved RNase, REGE-1, as a factor promoting fat accumulation. We found that REGE-1 controls fat by degrading mRNA encoding a fat loss-inducing transcription factor, ETS-4. Because ETS-4, in turn, stimulates rege-1 transcription, REGE-1 and ETS-4 form a dynamic, auto-regulatory module. Here, I propose to identify pathways regulating body fat through the ETS-4/REGE-1 module (ERM), determine how precisely the ERM induces fat loss, examine the conservation of ERM in mammalian adipocytes and interrogate chemical compounds inducing fat loss in C. elegans for similar effect on adipocytes. The ultimate goal is to identify novel targets for potential therapeutic intervention in the treatment of obesity-associated disorders.