Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*

Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*

Lysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons al...

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Main Authors: Grumet, Lukas, Eichmann, Thomas O., Taschler, Ulrike, Zierler, Kathrin A., Leopold, Christina, Moustafa, Tarek, Radovic, Branislav, Romauch, Matthias, Yan, Cong, Du, Hong, Haemmerle, Guenter, Zechner, Rudolf, Fickert, Peter, Kratky, Dagmar, Zimmermann, Robert, Lass, Achim
Format: Online
Language:English
Published: American Society for Biochemistry and Molecular Biology 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016185/
id pubmed-5016185
recordtype oai_dc
spelling pubmed-50161852016-09-16 Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover* Grumet, Lukas Eichmann, Thomas O. Taschler, Ulrike Zierler, Kathrin A. Leopold, Christina Moustafa, Tarek Radovic, Branislav Romauch, Matthias Yan, Cong Du, Hong Haemmerle, Guenter Zechner, Rudolf Fickert, Peter Kratky, Dagmar Zimmermann, Robert Lass, Achim Lipids Lysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons also contain retinyl esters (REs), a role of LAL in the clearance of endocytosed REs has not been reported. In this study, we found that murine LAL exhibits RE hydrolase activity. Pharmacological inhibition of LAL in the human hepatocyte cell line HepG2, incubated with chylomicrons, led to increased accumulation of REs in endosomal/lysosomal fractions. Furthermore, pharmacological inhibition or genetic ablation of LAL in murine liver largely reduced in vitro acid RE hydrolase activity. Interestingly, LAL-deficient mice exhibited increased RE content in the duodenum and jejunum but decreased RE content in the liver. Furthermore, LAL-deficient mice challenged with RE gavage exhibited largely reduced post-prandial circulating RE content, indicating that LAL is required for efficient nutritional vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis. American Society for Biochemistry and Molecular Biology 2016-08-19 2016-06-27 /pmc/articles/PMC5016185/ /pubmed/27354281 http://dx.doi.org/10.1074/jbc.M116.724054 Text en © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Grumet, Lukas
Eichmann, Thomas O.
Taschler, Ulrike
Zierler, Kathrin A.
Leopold, Christina
Moustafa, Tarek
Radovic, Branislav
Romauch, Matthias
Yan, Cong
Du, Hong
Haemmerle, Guenter
Zechner, Rudolf
Fickert, Peter
Kratky, Dagmar
Zimmermann, Robert
Lass, Achim
spellingShingle Grumet, Lukas
Eichmann, Thomas O.
Taschler, Ulrike
Zierler, Kathrin A.
Leopold, Christina
Moustafa, Tarek
Radovic, Branislav
Romauch, Matthias
Yan, Cong
Du, Hong
Haemmerle, Guenter
Zechner, Rudolf
Fickert, Peter
Kratky, Dagmar
Zimmermann, Robert
Lass, Achim
Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
author_facet Grumet, Lukas
Eichmann, Thomas O.
Taschler, Ulrike
Zierler, Kathrin A.
Leopold, Christina
Moustafa, Tarek
Radovic, Branislav
Romauch, Matthias
Yan, Cong
Du, Hong
Haemmerle, Guenter
Zechner, Rudolf
Fickert, Peter
Kratky, Dagmar
Zimmermann, Robert
Lass, Achim
author_sort Grumet, Lukas
title Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
title_short Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
title_full Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
title_fullStr Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
title_full_unstemmed Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover*
title_sort lysosomal acid lipase hydrolyzes retinyl ester and affects retinoid turnover*
description Lysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons also contain retinyl esters (REs), a role of LAL in the clearance of endocytosed REs has not been reported. In this study, we found that murine LAL exhibits RE hydrolase activity. Pharmacological inhibition of LAL in the human hepatocyte cell line HepG2, incubated with chylomicrons, led to increased accumulation of REs in endosomal/lysosomal fractions. Furthermore, pharmacological inhibition or genetic ablation of LAL in murine liver largely reduced in vitro acid RE hydrolase activity. Interestingly, LAL-deficient mice exhibited increased RE content in the duodenum and jejunum but decreased RE content in the liver. Furthermore, LAL-deficient mice challenged with RE gavage exhibited largely reduced post-prandial circulating RE content, indicating that LAL is required for efficient nutritional vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis.
publisher American Society for Biochemistry and Molecular Biology
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016185/
_version_ 1613646649269157888

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