Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
08
04
2020
received:
13
12
2019
accepted:
27
04
2020
pubmed:
28
5
2020
medline:
26
8
2021
entrez:
28
5
2020
Statut:
ppublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32460431
doi: 10.1002/hep.31391
pii: 01515467-202103000-00016
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1028-1044Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P01836X/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 19013
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC UU 12012/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K0019494/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K001949/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC MDU
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC UP A90 1006
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC PC 13030
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12077
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 19924
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011705/2
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 22585
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 23390
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18342/A23390
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R023026/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
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