Michele Vacca1,2, Julian L Griffin1,3, Zoe Hall1,3, Davide Chiarugi2, Evelina Charidemou1, Jack Leslie4, Emma Scott4, Luca Pellegrinet1, Michael Allison5, Gabriele Mocciaro1, Quentin M Anstee4,6, Gerard I Evan1, Matthew Hoare5,7, Antonio Vidal-Puig2, Fiona Oakley4. 1. Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom. 2. Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom. 3. Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom. 4. Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 5. Department of Medicine, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Cambridge, United Kingdom. 6. Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 7. CRUK Cambridge Institute, Robinson Way, Cambridge, United Kingdom.
Abstract
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.
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.
Authors: Elisabeth M Haberl; Rebekka Pohl; Lisa Rein-Fischboeck; Marcus Höring; Sabrina Krautbauer; Gerhard Liebisch; Christa Buechler Journal: Lipids Health Dis Date: 2021-10-10 Impact factor: 3.876
Authors: Marco Youssef William Zaki; Ahmed Khairallah Mahdi; Gillian Lucinda Patman; Quentin Mark Anstee; Dina Tiniakos; Anna Whitehead; João Pais Maurício; Misti Vanette McCain; Despina Televantou; Sameh Abou-Beih; Erik Ramon-Gil; Robyn Watson; Charlotte Cox; Jack Leslie; Caroline Wilson; Olivier Govaere; John Lunec; Derek Austin Mann; Sirintra Nakjang; Fiona Oakley; Ruchi Shukla; Helen Louise Reeves Journal: Sci Rep Date: 2021-08-18 Impact factor: 4.379
Authors: Natalia I Krupenko; Jaspreet Sharma; Halle M Fogle; Peter Pediaditakis; Kyle C Strickland; Xiuxia Du; Kristi L Helke; Susan Sumner; Sergey A Krupenko Journal: Cancers (Basel) Date: 2021-06-28 Impact factor: 6.575