Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success

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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.

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

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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.

"This ORCID iD identifies the author of this article:" 0000-0001-6858-408X
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.

"This ORCID iD identifies the author of this article:" 0000-0002-1565-7238
Harald F Hofbauer

Institute of Molecular Biosciences, University of Graz, Graz, Austria

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2617-5901
Wolfgang Mende

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Competing interests
The authors declare that no competing interests exist.
Ingrid Pörnbacher

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Competing interests
The authors declare that no competing interests exist.
Laura Schiller

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Competing interests
The authors declare that no competing interests exist.
Gabriele Schoiswohl

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Competing interests
The authors declare that no competing interests exist.
Hao Xie

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Competing interests
The authors declare that no competing interests exist.
Sebastian Grönke

Max Planck Institute for Biology of Ageing, Cologne, Germany

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1539-5346
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.

"This ORCID iD identifies the author of this article:" 0000-0002-5079-1109
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).

Copyright

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.