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Characterization of Lipid and Lipid Droplet Metabolism in Human HCC

Human hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with cirrhosis. While previous metabolic studies of HCC have mainly focused on the glucose metabolism (Warburg effect), less attention has been paid to tumor-sp...

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Autores principales: Berndt, Nikolaus, Eckstein, Johannes, Heucke, Niklas, Gajowski, Robert, Stockmann, Martin, Meierhofer, David, Holzhütter, Hermann-Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562484/
https://www.ncbi.nlm.nih.gov/pubmed/31137921
http://dx.doi.org/10.3390/cells8050512
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author Berndt, Nikolaus
Eckstein, Johannes
Heucke, Niklas
Gajowski, Robert
Stockmann, Martin
Meierhofer, David
Holzhütter, Hermann-Georg
author_facet Berndt, Nikolaus
Eckstein, Johannes
Heucke, Niklas
Gajowski, Robert
Stockmann, Martin
Meierhofer, David
Holzhütter, Hermann-Georg
author_sort Berndt, Nikolaus
collection PubMed
description Human hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with cirrhosis. While previous metabolic studies of HCC have mainly focused on the glucose metabolism (Warburg effect), less attention has been paid to tumor-specific features of the lipid metabolism. Here, we applied a computational approach to analyze major pathways of fatty acid utilization in individual HCC. To this end, we used protein intensity profiles of eleven human HCCs to parameterize tumor-specific kinetic models of cellular lipid metabolism including formation, enlargement, and degradation of lipid droplets (LDs). Our analysis reveals significant inter-tumor differences in the lipid metabolism. The majority of HCCs show a reduced uptake of fatty acids and decreased rate of β-oxidation, however, some HCCs display a completely different metabolic phenotype characterized by high rates of β-oxidation. Despite reduced fatty acid uptake in the majority of HCCs, the content of triacylglycerol is significantly enlarged compared to the tumor-adjacent tissue. This is due to tumor-specific expression profiles of regulatory proteins decorating the surface of LDs and controlling their turnover. Our simulations suggest that HCCs characterized by a very high content of triglycerides comprise regulatory peculiarities that render them susceptible to selective drug targeting without affecting healthy tissue.
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spelling pubmed-65624842019-06-17 Characterization of Lipid and Lipid Droplet Metabolism in Human HCC Berndt, Nikolaus Eckstein, Johannes Heucke, Niklas Gajowski, Robert Stockmann, Martin Meierhofer, David Holzhütter, Hermann-Georg Cells Article Human hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with cirrhosis. While previous metabolic studies of HCC have mainly focused on the glucose metabolism (Warburg effect), less attention has been paid to tumor-specific features of the lipid metabolism. Here, we applied a computational approach to analyze major pathways of fatty acid utilization in individual HCC. To this end, we used protein intensity profiles of eleven human HCCs to parameterize tumor-specific kinetic models of cellular lipid metabolism including formation, enlargement, and degradation of lipid droplets (LDs). Our analysis reveals significant inter-tumor differences in the lipid metabolism. The majority of HCCs show a reduced uptake of fatty acids and decreased rate of β-oxidation, however, some HCCs display a completely different metabolic phenotype characterized by high rates of β-oxidation. Despite reduced fatty acid uptake in the majority of HCCs, the content of triacylglycerol is significantly enlarged compared to the tumor-adjacent tissue. This is due to tumor-specific expression profiles of regulatory proteins decorating the surface of LDs and controlling their turnover. Our simulations suggest that HCCs characterized by a very high content of triglycerides comprise regulatory peculiarities that render them susceptible to selective drug targeting without affecting healthy tissue. MDPI 2019-05-27 /pmc/articles/PMC6562484/ /pubmed/31137921 http://dx.doi.org/10.3390/cells8050512 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Berndt, Nikolaus
Eckstein, Johannes
Heucke, Niklas
Gajowski, Robert
Stockmann, Martin
Meierhofer, David
Holzhütter, Hermann-Georg
Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title_full Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title_fullStr Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title_full_unstemmed Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title_short Characterization of Lipid and Lipid Droplet Metabolism in Human HCC
title_sort characterization of lipid and lipid droplet metabolism in human hcc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562484/
https://www.ncbi.nlm.nih.gov/pubmed/31137921
http://dx.doi.org/10.3390/cells8050512
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