Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success

  1. Christoph Heier  Is a corresponding author
  2. Oskar Knittelfelder
  3. Harald F Hofbauer
  4. Wolfgang Mende
  5. Ingrid Pörnbacher
  6. Laura Schiller
  7. Gabriele Schoiswohl
  8. Hao Xie
  9. Sebastian Grönke
  10. Andrej Shevchenko
  11. Ronald P Kühnlein
  1. University of Graz, Austria
  2. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  3. Max Planck Institute for Biology of Ageing, Germany

Abstract

Triacylglycerol (TG) and steryl ester (SE) lipid storage is a universal strategy to maintain organismal energy and membrane homeostasis. Cycles of building and mobilizing storage fat are fundamental in (re)distributing lipid substrates between tissues or to progress ontogenetic transitions. In this study we show that Hormone-sensitive lipase (Hsl) specifically controls SE mobilization to initiate intergenerational sterol transfer in Drosophila melanogaster. Tissue-autonomous Hsl functions in the maternal fat body and germline coordinately prevent adult SE overstorage and maximize sterol allocation to embryos. While Hsl-deficiency is largely dispensable for normal development on sterol-rich diets, animals depend on adipocyte Hsl for optimal fecundity when dietary sterol becomes limiting. Notably, accumulation of SE but not of TG is a characteristic of Hsl-deficient cells across phyla including murine white adipocytes. In summary, we identified Hsl as an ancestral regulator of SE degradation, which improves intergenerational sterol transfer and reproductive success in flies.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Christoph Heier

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    For correspondence
    christoph.heier@uni-graz.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6858-408X
  2. Oskar Knittelfelder

    Shevchenko lab, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1565-7238
  3. Harald F Hofbauer

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2617-5901
  4. Wolfgang Mende

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Ingrid Pörnbacher

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Laura Schiller

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Gabriele Schoiswohl

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Hao Xie

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Sebastian Grönke

    Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1539-5346
  10. Andrej Shevchenko

    Shevchenko lab, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5079-1109
  11. Ronald P Kühnlein

    Institute of Molecular Biosciences, University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.

Funding

Austrian Science Fund (P28882-B21)

  • Gabriele Schoiswohl

Deutsche Forschungsgemeinschaft (FOR 2682)

  • Andrej Shevchenko

Deutsche Forschungsgemeinschaft (TRR83 (TP17))

  • Andrej Shevchenko

Austrian Science Fund (M 2706-B34)

  • Ingrid Pörnbacher

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal protocols were approved by the Austrian Federal Ministry for Science, Research, and Economy (protocol number BMWFW-66.007/0026/-WF/V/3b/2017) and the ethics committee of the University of Graz, and were conducted in compliance with the council of Europe Convention (ETS 123).

Reviewing Editor

  1. Joel K Elmquist, University of Texas Southwestern Medical Center, United States

Version history

  1. Received: September 28, 2020
  2. Accepted: February 3, 2021
  3. Accepted Manuscript published: February 4, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2021, Heier 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. Christoph Heier
  2. Oskar Knittelfelder
  3. Harald F Hofbauer
  4. Wolfgang Mende
  5. Ingrid Pörnbacher
  6. Laura Schiller
  7. Gabriele Schoiswohl
  8. Hao Xie
  9. Sebastian Grönke
  10. Andrej Shevchenko
  11. Ronald P Kühnlein
(2021)
Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success
eLife 10:e63252.
https://doi.org/10.7554/eLife.63252

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