ANALYSIS OF GENETIC AND NEURONAL CIRCUITS OF FAT AND FEEDING
A major challenge in biology is to understand how gene products form dynamic networks that operate in multiple tissues to coordinate physiology. One such network is the set of genes that determine the balance between energy intake and utilization. Fat regulation involves a complex interplay between feeding centers in the nervous system and the transport, storage and mobilization of fat in the periphery. Defects in energy balance are associated with metabolic disorders, cardiovascular disease, and cancers.
Using mutagenesis and genome-wide RNAi studies, we previously identified over 400 genes that regulate fat levels in C. elegans. These include components of neuroendocrine signaling, channels and transporters, transcription, metabolism and many genes with previously unassigned functions. Our findings highlight the shared ancestry of C. elegans and mammalian fat regulation. More importantly, this work identifies hundreds of new genes that participate in novel fat regulatory pathways. We have now undertaken the daunting task of understanding the modes of function of these fat regulatory genes within the context of intact organisms. These genes affect functions as diverse as metabolism and behavior.