A Novel C. elegans Model for Studying Adiponectin Receptor Signaling
Diabetes is a chronic disease characterized by high blood sugar. Adiponectin is blood-circulating protein hormone with potent anti-diabetic and anti-inflammatory properties in mammals. This project establishes a new research paradigm for studies of adiponetin receptor signaling in C. elegans, an invertebrate nematode. We identified a previous uncloned C. elegans gene egl-25 as a C. elegans homolog of the mammalian AdipoR2. EGL-25 regulates the transcription factor NHR-49, as AdipoR2 regulates PPARa, the mammalian counterpart of NHR-49. The major goals of this project are to elucidate the genetic mechanisms by which EGL-25 regulates NHR-49 in C. elegans and to evaluate the functional conservation and similarity of the C. elegans EGL-25/NHR-49 pathway to the AdipR2/PPARa pathway in mammalian cells. Results from this project should identify new regulators and mechanisms of action of AdipoRs and provide possible therapeutic targets to treat diabetes and its associated metabolic and cardiovascular disorders.