Distinct Role of Nuclear Receptor Corepressor 1 Regulated De Novo Fatty Acids Synthesis in Liver Regeneration and Hepatocarcinogenesis in Mice
| Autor: | Qing Ou-Yang, Feng Huo, Qibin Leng, Bo Zheng, Hongyang Wang, Xin Chen, Frank J. Gonzalez, Liang Li, Yingcheng Yang, Xiaoqing Jiang, Lei Chen, Guojun Hou, Yanjing Zhu, Guijuan Luo, Xi-Meng Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Carcinogenesis Apoptosis Mitochondrion Biology Article 03 medical and health sciences Mice Animals Nuclear Receptor Co-Repressor 1 Nuclear receptor co-repressor 1 Cell Proliferation Mice Knockout Hepatology Regeneration (biology) Lipogenesis Fatty Acids Liver regeneration Cell biology Liver Regeneration 030104 developmental biology Nuclear receptor Biochemistry Liver Hepatocytes |
| Popis: | It is urgent that the means to improve liver regeneration (LR) be found, while mitigating the concurrent risk of hepatocarcinogenesis (HCG). Nuclear receptor corepressor 1 (NCoR1) is a co-repressor of nuclear receptors, which regulates the expression level of metabolic genes; however, little is known about its potential contribution for LR and HCG. Here, we found that liver-specific NCoR1 knockout in mice (NCoR1(Δhep)) dramatically enhances LR after partial hepatectomy and, surprisingly, blocks the process of diethylnitrosamine (DEN)-induced HCG. Both RNA-sequencing and metabolic assay results revealed improved expression of Fasn and Acc2 in NCoR1(Δhep) mice, suggesting the critical role of de novo fatty acid synthesis (FAS) in LR. Continual enhanced de novo FAS in NCoR1(Δhep) mice resulted in overwhelmed adenosine triphosphate ATP and nicotinamide adenine dinucleotide phosphate (NADPH) consumption and increased mitochondrial reactive oxygen species production, which subsequently attenuated HCG through inducing apoptosis of hepatocytes at an early stage after DEN administration. Conclusion: NCoR1 functions as a negative modulator for hepatic de novo FAS and mitochondria energy adaptation, playing distinct roles in regeneration or carcinogenesis. |
| Databáze: | OpenAIRE |
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