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- Title
Polygenic control of Caenorhabditis elegans fat storage.
- Authors
Ho Yi Mak; Nelson, Laura S.; Basson, Michael; Johnson, Carl D.; Ruvkun, Gary
- Abstract
Tubby mice and individuals with Bardet-Biedl syndrome have defects in ciliated neuron function and obesity, suggesting an as-yet unknown metabolic signaling axis from ciliated neurons to fat storage tissues. Here we show coordinate regulation of Caenorhabditis elegans fat storage by orthologues of these genes acting in ciliated neurons and by a 3-ketoacyl-coA thiolase (encoded by kat-1) that acts in fat storage tissue. A genetic screen for markedly enhanced fat storage in tub-1 mutants led to the isolation only of kat-1 alleles, which impair fatty acid β-oxidation. kat-1 acts in the intestine, the major C. elegans fat storage tissue, and is transcriptionally upregulated in animals with high fat storage. A genetic screen for synergistic increase in fat storage of a kat-1 mutant identified bbs-1. bbs-1 acts in 15 ciliated neurons that are poised to sense external and internal nutrient levels, supporting a model in which bbs-1 and tub-1 in ciliated neurons form part of an ancient, conserved neuroendocrine axis. This pathway also includes genes encoding intraflagellar transport proteins and cyclic nucleotide gated channels, demonstrating that C. elegans fat storage is under polygenic control.
- Publication
Nature Genetics, 2006, Vol 38, Issue 3, p363
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng1739