Metabolic Analysis of the Cultured Hepatic Cell Persistently Infected with Hepatitis C Virus

本研究建立了丙型肝炎病毒（HCV）持续感染的肝细胞系HPI细胞，以探讨HCV引起肝细胞代谢改变的机制。该细胞系积累大量脂滴，显示显著的脂肪变性。因此，我们将微阵列和代谢组学结合起来进行综合分析。因此，通过上调限速酶来增强胆固醇和脂肪酸的产生。戊糖磷酸途径随着NADPH的产生而增强。此外，TCA循环也增强，表明HPI细胞的高代谢状态。推测HPI细胞的高代谢可能与其组成性激活的代谢关键转录因子Nrf2有关，因此HPI细胞不仅是研究HCV的重要工具，也是研究肝脏代谢的重要工具。

In this study, to explore the mechanism for metabolic alteration by hepatisis C virus (HCV), we established a hepatic cell line, HPI cell, persistently infected with HCV. This cell line accumulated massive lipid droplets showing prominent steatosis. Thus we performed integrated analysis by combining microarray and metabolomics. As a result, enhanced production of cholesterol and fatty acids by up-regulation of the rate limiting enzymes. Pentose phosphate pathway was enhanced with production of NADPH. Moreover, TCA cycle was also enhanced indicating hypermetabolic status of the HPI cell. It was speculated that constitutively activated Nrf2, which is a key transcription factor for metabolism, was attributed to the hypermetabolism of HPI cell.In conclusion, HPI cell is a useful tool for research of not only HCV but also liver metabolism.