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How do networks of genes function at the organismal level? Fat regulation involves a complex interplay between the feeding regulatory centers in the nervous system and sites of fat storage. Using genetic and genome-wide RNAi approaches, we have identified over 400 genes that affect C. elegans fat content. These include components of neuroendocrine signaling, transcription, metabolism, and novel pathways. Our broad aims are i) to understand the molecular functions and modes of regulation of the newly identified genes in the context of living animals, ii) to determine how development, environment, and disease associated genes affect the fat regulatory network, iii) to determine how food sensation and metabolism are coupled, and iv) to delineate the neuronal networks that regulate feeding behavior. In collaborative efforts we are extending our findings to help identify genes that underlie diabetes and obesity related disorders.