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Abstract Details
Lipid Remodelling in Hepatocyte Proliferation and Hepatocellular Carcinoma
Hepatology. 2020 May 27. doi: 10.1002/hep.31391. Online ahead of print.
Zoe Hall12, Davide Chiarugi3, Evelina Charidemou1, Jack Leslie4, Emma Scott4, Luca Pelligrinet1, Michael Allison5, Gabriele Mocciaro1, Quentin M Anstee46, Gerard I Evan1, Matthew Hoare57, Antonio Vidal-Puig3, Fiona Oakley4, Michele Vacca13, Julian L Griffin12
Author information
1Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
2Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
3Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom.
4Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
5Department of Medicine, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
6Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
7CRUK Cambridge Institute, Robinson Way, Cambridge, United Kingdom.
Abstract
Background & 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 & 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.
Conclusion: 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 new therapeutic strategies and prognostic biomarkers of HCC.