Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success.

Christoph Heier,Hao Xie,Wolfgang Mende,Oskar Knittelfelder,Harald F Hofbauer,Ronald P Kühnlein,Laura Schiller,Andrej Shevchenko,Gabriele Schoiswohl,Sebastian Grönke,Ingrid Pörnbacher

doi:10.7554/elife.63252

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.

Highlights

Lipids fulfill essential functions as energy carriers, membrane components, and signal molecules
We assessed the subcellular localization of a fluorescently-tagged version of Hormone-sensitive lipase (Hsl) (Hsl-EGFP) in fat body cells of adult flies and found that Hsl-EGFP concentrated at the surface of lipid droplets (LDs) (Figure 1D)
Our data show that Hsl is a LD-associated multifunctional lipid ester hydrolase, which implies a function of the enzyme in Drosophila storage lipid breakdown

Summary

Introduction

Lipids fulfill essential functions as energy carriers, membrane components, and signal molecules. Mobilization of this storage lipid depots initiates transfer of FAs to non-adipose tissues for energy production (Azeez et al, 2014; Lafontan and Langin, 2009). To cope with fluctuations in nutrient availability, Drosophila deposits large amounts of storage lipids in the fat body, which shares many lipid metabolic functions with mammalian adipose tissue and liver, and serves as major nutrient reservoir (Arrese and Soulages, 2010). Hsl is a TG and major DG lipase in mammalian adipocytes where it acts in parallel and downstream of ATGL to promote storage lipid breakdown (Lass et al, 2011). In an effort to understand how lipid hydrolases control inter-tissue lipid homeostasis, we characterized the molecular and physiological functions of the single Hsl ortholog of Drosophila. By initiating SE breakdown, Hsl promotes efficient sterol transfer from mothers to progeny and increases the embryonic sterol content during Drosophila development to support reproductive success

Results

Discussion

Materials and methods

Funding Funder Austrian Science Fund