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Taschler, U; Schreiber, R; Chitraju, C; Grabner, GF; Romauch, M; Wolinski, H; Haemmerle, G; Breinbauer, R; Zechner, R; Lass, A; Zimmermann, R.
Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells.
Biochim Biophys Acta. 2015; 1851(7):937-45
Doi: 10.1016/j.bbalip.2015.02.017
[OPEN ACCESS]
Web of Science
PubMed
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- Leading authors Med Uni Graz
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Taschler Ulrike
- Co-authors Med Uni Graz
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Grabner Gernot
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Romauch Matthias
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Schreiber Renate
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- Abstract:
- Hepatic stellate cells (HSCs) store triglycerides (TGs) and retinyl ester (RE) in cytosolic lipid droplets. RE stores are degraded following retinoid starvation or in response to pathogenic stimuli resulting in HSC activation. At present, the major enzymes catalyzing lipid degradation in HSCs are unknown. In this study, we investigated whether adipose triglyceride lipase (ATGL) is involved in RE catabolism of HSCs. Additionally, we compared the effects of ATGL deficiency and hormone-sensitive lipase (HSL) deficiency, a known RE hydrolase (REH), on RE stores in liver and adipose tissue. We show that ATGL degrades RE even in the presence of TGs, implicating that these substrates compete for ATGL binding. REH activity was stimulated and inhibited by comparative gene identification-58 and G0/G1 switch gene-2, respectively, the physiological regulators of ATGL activity. In cultured primary murine HSCs, pharmacological inhibition of ATGL, but not HSL, increased RE accumulation. In mice globally lacking ATGL or HSL, RE contents in white adipose tissue were decreased or increased, respectively, while plasma retinol and liver RE levels remained unchanged. In conclusion, our study shows that ATGL acts as REH in HSCs promoting the degradation of RE stores in addition to its established function as TG lipase. HSL is the predominant REH in adipocytes but does not affect lipid mobilization in HSCs.
- Find related publications in this database (using NLM MeSH Indexing)
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Adipocytes - enzymology, metabolism
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Animals - administration & dosage
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COS Cells - administration & dosage
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Carboxylic Ester Hydrolases - genetics, metabolism
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Chlorocebus aethiops - administration & dosage
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Female - administration & dosage
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Hepatic Stellate Cells - metabolism
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Lipase - physiology
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Lipid Metabolism - genetics
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Mice - administration & dosage
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Mice, Knockout - administration & dosage
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Retinoids - metabolism
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Sterol Esterase - genetics, metabolism
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Triglycerides - metabolism
- Find related publications in this database (Keywords)
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Adipose triglyceride lipase
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Hepatic stellate cells
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Retinoids
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Retinyl ester