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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6562484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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