Lysosomal acid lipase hydrolyzes retinyl ester and affects retinoid turnover

Lukas Grumet, Thomas O. Eichmann, Ulrike Taschler, Kathrin A. Zierler, Christina Leopold, Tarek Moustafa, Branislav Radovic, Matthias Romauch, Cong Yan, Hong Du, Guenter Haemmerle, Rudolf Zechner, Peter Fickert, Dagmar Kratky, Robert Zimmermann, Achim Lass

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 vitaminAavailability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis.

Original languageEnglish (US)
Pages (from-to)17977-17987
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number34
DOIs
StatePublished - Aug 19 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Grumet, L., Eichmann, T. O., Taschler, U., Zierler, K. A., Leopold, C., Moustafa, T., Radovic, B., Romauch, M., Yan, C., Du, H., Haemmerle, G., Zechner, R., Fickert, P., Kratky, D., Zimmermann, R., & Lass, A. (2016). Lysosomal acid lipase hydrolyzes retinyl ester and affects retinoid turnover. Journal of Biological Chemistry, 291(34), 17977-17987. https://doi.org/10.1074/jbc.M116.724054