Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success
- University of Graz, Austria
- Max Planck Institute of Molecular Cell Biology and Genetics, Germany
- 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
Oskar Knittelfelder
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
© 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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Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success
eLife 10:e63252.
https://doi.org/10.7554/eLife.63252
Further reading
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Teichoic acids (TA) are linear phospho-saccharidic polymers and important constituents of the cell envelope of Gram-positive bacteria, either bound to the peptidoglycan as wall teichoic acids (WTA) or to the membrane as lipoteichoic acids (LTA). The composition of TA varies greatly but the presence of both WTA and LTA is highly conserved, hinting at an underlying fundamental function that is distinct from their specific roles in diverse organisms. We report the observation of a periplasmic space in Streptococcus pneumoniae by cryo-electron microscopy of vitreous sections. The thickness and appearance of this region change upon deletion of genes involved in the attachment of TA, supporting their role in the maintenance of a periplasmic space in Gram-positive bacteria as a possible universal function. Consequences of these mutations were further examined by super-resolved microscopy, following metabolic labeling and fluorophore coupling by click chemistry. This novel labeling method also enabled in-gel analysis of cell fractions. With this approach, we were able to titrate the actual amount of TA per cell and to determine the ratio of WTA to LTA. In addition, we followed the change of TA length during growth phases, and discovered that a mutant devoid of LTA accumulates the membrane-bound polymerized TA precursor.
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