title: Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence.
abstract: In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question of how these effects might be related. Here, we show that a lack of GSCs results in a broad transcriptional reprogramming in which the conserved detoxification regulator SKN-1/Nrf increases stress resistance, proteasome activity, and longevity. SKN-1 also activates diverse lipid metabolism genes and reduces fat storage, thereby alleviating the increased fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by signals from this fat, which appears to derive from unconsumed yolk that was produced for reproduction. We conclude that SKN-1 plays a direct role in maintaining lipid homeostasis in which it is activated by lipids. This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease and suggest that particular endogenous or dietary lipids might promote health through SKN-1/Nrf.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0002-2403-2221
authors.initials: MJ
authors.lastname: Steinbaugh
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Sri Devi
authors.initials: SD
authors.lastname: Narasimhan
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Stacey
authors.initials: S
authors.lastname: Robida-Stubbs
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Lorenza E
authors.initials: LE
authors.lastname: Moronetti Mazzeo
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Dreyfuss
authors.affiliation: Department of Genetics and Harvard Stem Cell Institute, Harvard Medical School, Boston, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Hourihan
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Prashant
authors.initials: P
authors.lastname: Raghavan
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Operaña
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: Reza
authors.initials: R
authors.lastname: Esmaillie
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, United States.
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000502:physiology*; D050356:Lipid Metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans
keywords: C. elegans; SKN-1/Nrf; aging; cell biology; chromosomes; fatty acid signaling; genes; germline stem cells; lipid metabolism; proteostasis