Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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):17977-87
Doi: 10.1074/jbc.M116.724054
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- Co-authors Med Uni Graz
- Eichmann Thomas
- Fickert Peter
- Kratky Dagmar
- Leopold Christina
- Moustafa Tarek
- Radovic Branislav
- Romauch Matthias
- Taschler Ulrike
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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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Carboxylic Ester Hydrolases - genetics, metabolism
- Cholesterol Esters - genetics, metabolism
- Chylomicron Remnants - genetics, metabolism
- Duodenum - enzymology
- Humans - administration & dosage
- Jejunum - enzymology
- Mice - administration & dosage
- Mice, Knockout - administration & dosage
- Retinoids - genetics, metabolism
- Sterol Esterase - genetics, metabolism
- Triglycerides - genetics, metabolism
- Find related publications in this database (Keywords)
- hydrolase
- lipase
- retinoid
- retinol
- vitamin A
- knockout mouse
- lysosomal acid lipase
- retinyl ester