Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma
Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma
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DOI：
10.1002/hep.31391
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发表时间：
2020-11-03
期刊：
影响因子：
13.5
通讯作者：
Griffin, Julian L.
中科院分区：
文献类型：
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作者：
Hall, Zoe;Chiarugi, Davide;Griffin, Julian L.
背景和目的 在代偿性再生和肝细胞癌 (HCC) 过程中，肝细胞在准备增殖时会经历深刻的代谢重组。然而，这些过程的代谢控制尚不完全清楚。为了捕获增殖肝细胞的代谢特征，我们将最先进的系统生物学方法应用于肝再生、药理学和基因激活细胞增殖以及 HCC 模型。方法和结果整合代谢组学、脂质组学和转录组学，我们将增殖肝细胞脂质组的变化与改变的代谢途径联系起来，包括脂肪生成、脂肪酸去饱和和磷脂酰胆碱 (PC) 的生成。我们证实了人类 HCC 中脂质特征的这种改变，并显示单不饱和 PC 与细胞增殖和肝癌发生的标志呈正相关。结论总的来说，我们证明当肝细胞转向增殖时，特定的脂质代谢途径会发生连贯改变。这些代表了 HCC 治疗策略和预后生物标志物开发的靶标来源。
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.