Wagner_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1865_158730

Reference

Title : Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation - Wagner_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1865_158730
Author(s) : Wagner C , Hois V , Pajed L , Pusch LM , Wolinski H , Trauner M , Zimmermann R , Taschler U , Lass A
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , 1865 :158730 , 2020
Abstract :

Vitamin A is stored as retinyl esters (REs) in lipid droplets of hepatic stellate cells (HSCs). To date, two different pathways are known to facilitate the breakdown of REs: (i) Hydrolysis of REs by neutral lipases, and (ii) whole lipid droplet degradation in autolysosomes by acid hydrolysis. In this study, we evaluated the contribution of neutral and acid RE hydrolases to the breakdown of REs in human HSCs. (R)-Bromoenol lactone (R-BEL), inhibitor of adipose triglyceride lipase (ATGL) and patatin-like phospholipase domain-containing 3 (PNPLA3), the hormone-sensitive lipase (HSL) inhibitor 76-0079, as well as the serine-hydrolase inhibitor Orlistat reduced neutral RE hydrolase activity of LX-2 cell-lysates between 20 and 50%. Interestingly, in pulse-chase experiments, R-BEL, 76-0079, as well as Orlistat exerted little to no effect on cellular RE breakdown of LX-2 cells as well as primary human HSCs. In contrast, Lalistat2, a specific lysosomal acid lipase (LAL) inhibitor, virtually blunted acid in vitro RE hydrolase activity of LX-2 cells. Accordingly, HSCs isolated from LAL-deficient mice showed RE accumulation and were virtually devoid of acidic RE hydrolase activity. In pulse-chase experiments however, LAL-deficient HSCs, similar to LX-2 cells and primary human HSCs, were not defective in degrading REs. In summary, results demonstrate that ATGL, PNPLA3, and HSL contribute to neutral RE hydrolysis of human HSCs. LAL is the major acid RE hydrolase in HSCs. Yet, LAL is not limiting for RE degradation under serum-starvation. Together, results suggest that RE breakdown of HSCs is facilitated by (a) so far unknown, non-Orlistat inhibitable RE-hydrolase(s).

PubMedSearch : Wagner_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1865_158730
PubMedID: 32361002
Gene_locus related to this paper: human-LIPA

Related information

Inhibitor (R)-BEL    76-0079    Lalistat-2    Orlistat
Substrate Retinol-palmitate
Gene_locus human-LIPA

Citations formats

Wagner C, Hois V, Pajed L, Pusch LM, Wolinski H, Trauner M, Zimmermann R, Taschler U, Lass A (2020)
Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation
Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids 1865 :158730

Wagner C, Hois V, Pajed L, Pusch LM, Wolinski H, Trauner M, Zimmermann R, Taschler U, Lass A (2020)
Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids 1865 :158730