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Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells
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 un...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Pub. Co
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408194/ https://www.ncbi.nlm.nih.gov/pubmed/25732851 http://dx.doi.org/10.1016/j.bbalip.2015.02.017 |
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author | Taschler, Ulrike Schreiber, Renate Chitraju, Chandramohan Grabner, Gernot F. Romauch, Matthias Wolinski, Heimo Haemmerle, Guenter Breinbauer, Rolf Zechner, Rudolf Lass, Achim Zimmermann, Robert |
author_facet | Taschler, Ulrike Schreiber, Renate Chitraju, Chandramohan Grabner, Gernot F. Romauch, Matthias Wolinski, Heimo Haemmerle, Guenter Breinbauer, Rolf Zechner, Rudolf Lass, Achim Zimmermann, Robert |
author_sort | Taschler, Ulrike |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4408194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Pub. Co |
record_format | MEDLINE/PubMed |
spelling | pubmed-44081942015-07-01 Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells Taschler, Ulrike Schreiber, Renate Chitraju, Chandramohan Grabner, Gernot F. Romauch, Matthias Wolinski, Heimo Haemmerle, Guenter Breinbauer, Rolf Zechner, Rudolf Lass, Achim Zimmermann, Robert Biochim Biophys Acta Article 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. Elsevier Pub. Co 2015-07 /pmc/articles/PMC4408194/ /pubmed/25732851 http://dx.doi.org/10.1016/j.bbalip.2015.02.017 Text en © 2015 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Taschler, Ulrike Schreiber, Renate Chitraju, Chandramohan Grabner, Gernot F. Romauch, Matthias Wolinski, Heimo Haemmerle, Guenter Breinbauer, Rolf Zechner, Rudolf Lass, Achim Zimmermann, Robert Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title | Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title_full | Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title_fullStr | Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title_full_unstemmed | Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title_short | Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
title_sort | adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408194/ https://www.ncbi.nlm.nih.gov/pubmed/25732851 http://dx.doi.org/10.1016/j.bbalip.2015.02.017 |
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