Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma
| Autor: | Jack Leslie, Michael Allison, Fiona Oakley, Gabriele Mocciaro, Matthew Hoare, Luca Pellegrinet, Julian L. Griffin, Evelina Charidemou, Quentin M. Anstee, Michele Vacca, Antonio Vidal-Puig, Davide Chiarugi, Gerard I. Evan, Emma Scott, Zoe Hall |
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| Přispěvatelé: | Hall, Zoe [0000-0002-1434-8329], Leslie, Jack [0000-0001-6443-2396], Pellegrinet, Luca [0000-0003-2081-8531], Anstee, Quentin M [0000-0002-9518-0088], Hoare, Matthew [0000-0001-5990-9604], Vidal-Puig, Antonio [0000-0003-4220-9577], Griffin, Julian L [0000-0003-1336-7744], Apollo - University of Cambridge Repository, Medical Research Council, Medical Research Council (MRC) |
| Rok vydání: | 2020 |
| Předmět: |
EXPRESSION
Male 0301 basic medicine LIVER Carcinoma Hepatocellular PROGRESSION METABOLISM Biology Mice 03 medical and health sciences 0302 clinical medicine Lipidomics medicine Animals Humans Metabolomics SIGNATURES Cell Proliferation Science & Technology ROLES Gastroenterology & Hepatology FATTY-ACID Hepatology Cell growth Gene Expression Profiling Lipogenesis Liver Neoplasms NASH 1103 Clinical Sciences Lipid metabolism Lipidome Lipid Metabolism CANCER Liver regeneration 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 1101 Medical Biochemistry and Metabolomics 1107 Immunology Hepatocyte Metabolic control analysis Hepatocytes Cancer research 030211 gastroenterology & hepatology Life Sciences & Biomedicine Metabolic Networks and Pathways |
| Zdroj: | Hepatology |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.31391 |
| Popis: | Background and aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically and genetically activated cell proliferation, and HCC.Approach and results: Integrating metabolomics, lipidomics, and transcriptomics, we link changes in the lipidome of proliferating hepatocytes to altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC). We confirm this altered lipid signature in human HCC and show a positive correlation of monounsaturated PC with hallmarks of cell proliferation and hepatic carcinogenesis.Conclusions: Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of therapeutic strategies and prognostic biomarkers of HCC. |
| Databáze: | OpenAIRE |
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