Abstract

In C. 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 suggests that particular endogenous or dietary lipids might promote health through SKN-1/Nrf.

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Author details

  1. Michael J Steinbaugh

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sri Devi Narasimhan

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stacey Robida-Stubbs

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lorenza E Moronetti Mazzeo

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jonathan M Dreyfuss

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. John M Hourihan

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Prashant Raghavan

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Theresa N Operaña

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Reza Esmaillie

    Research Division, Joslin Diabetes Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. T Keith Blackwell

    Research Division, Joslin Diabetes Center, Boston, United States
    For correspondence
    keith.blackwell@joslin.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Kang Shen, Howard Hughes Medical Institute, Stanford University, United States

Version history

  1. Received: March 31, 2015
  2. Accepted: July 9, 2015
  3. Accepted Manuscript published: July 21, 2015 (version 1)
  4. Version of Record published: August 19, 2015 (version 2)
  5. Version of Record updated: January 25, 2017 (version 3)

Copyright

© 2015, Steinbaugh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Michael J Steinbaugh
  2. Sri Devi Narasimhan
  3. Stacey Robida-Stubbs
  4. Lorenza E Moronetti Mazzeo
  5. Jonathan M Dreyfuss
  6. John M Hourihan
  7. Prashant Raghavan
  8. Theresa N Operaña
  9. Reza Esmaillie
  10. T Keith Blackwell
(2015)
Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence
eLife 4:e07836.
https://doi.org/10.7554/eLife.07836

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https://doi.org/10.7554/eLife.07836

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