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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Grumet, L; Eichmann, TO; Taschler, U; Zierler, KA; Leopold, C; Moustafa, T; Radovic, B; Romauch, M; Yan, C; Du, H; Haemmerle, G; Zechner, R; Fickert, P; Kratky, D; Zimmermann, R; Lass, A.
Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover.
J Biol Chem. 2016; 291(34):17977-17987 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Fickert Peter
Kratky Dagmar
Leopold Christina
Moustafa Tarek
Radovic Branislav
Romauch Matthias
Taschler Ulrike
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Number of Figures: 7
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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 vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Carboxylic Ester Hydrolases - genetics
Carboxylic Ester Hydrolases - metabolism
Cholesterol Esters - genetics
Cholesterol Esters - metabolism
Chylomicron Remnants - genetics
Chylomicron Remnants - metabolism
Duodenum - enzymology
Humans -
Jejunum - enzymology
Mice -
Mice, Knockout -
Retinoids - genetics
Retinoids - metabolism
Sterol Esterase - genetics
Sterol Esterase - metabolism
Triglycerides - genetics
Triglycerides - metabolism

Find related publications in this database (Keywords)
hydrolase
lipase
retinoid
retinol
vitamin A
knockout mouse
lysosomal acid lipase
retinyl ester
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