Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence
- Joslin Diabetes Center, United States
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.
Article and author information
Author details
Reviewing Editor
- Kang Shen, Howard Hughes Medical Institute, Stanford University, United States
Version history
- Received: March 31, 2015
- Accepted: July 9, 2015
- Accepted Manuscript published: July 21, 2015 (version 1)
- Version of Record published: August 19, 2015 (version 2)
- 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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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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