Simillion Cedric, Semmo Nasser, Idle Jeffrey R, Beyoğlu Diren
Interfaculty Bioinformatics Unit and SIB Swiss Institute of Bioinformatics, University of Bern, Baltzerstrasse 6, 3012 Bern, Switzerland.
Department of BioMedical Research, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
Metabolites. 2017 Oct 8;7(4):51. doi: 10.3390/metabo7040051.
About one in 15 of the world's population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.
全球约十五分之一的人口长期感染乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV），这带来了巨大的公共卫生后果。这些感染所引起的代谢改变从未被直接比较和对比过。我们使用气相色谱 - 质谱分析法对HBV阳性、HCV阳性和未感染的健康对照组的血浆和尿液进行了研究。对代谢物数据进行了稳健回归分析，以揭示代谢物对之间的相关性。HBV血浆和尿液中有10种代谢物相关性，HCV血浆和尿液中有18种，而对照组中均不存在这些相关性。构建了代谢扰动网络，从而能够对HBV和HCV感染的肝脏有不同的认识。HBV肝炎与葡萄糖摄取增加、糖酵解和磷酸戊糖途径代谢增强一致，后者利用木糖醇并产生苏糖酸，苏糖酸也可能由葡萄糖转运体导入。HCV肝炎与葡萄糖摄取受损、糖酵解和磷酸戊糖途径代谢受损一致，三羧酸途径由支链氨基酸供能以促进糖异生，肝细胞葡萄糖流失，这很可能导致了高血糖。结论是，稳健回归分析能够揭示疾病状态下的代谢重编程。
