Sandlers Yana, Shah Rohan R, Pearce Ryan W, Dasarathy Jaividhya, McCullough Arthur J, Dasarathy Srinivasan
Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA.
MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, 44139, USA.
J Clin Med. 2020 Jan 22;9(2):314. doi: 10.3390/jcm9020314.
Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD ( = 22) and matched control ( = 67) cohorts. Circulating levels of isocitrate and citrate were significantly ( < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson's correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.
非酒精性肝病（NAFLD）表现出广泛的临床症状，并且与代谢综合征、炎症和线粒体功能障碍密切相关。尽管NAFLD中线粒体功能障碍的机制仍未完全阐明，但多项研究已证明NAFLD中存在分子、生化和生物物理线粒体异常的证据。鉴于NAFLD与线粒体功能障碍之间的关联，本研究的目的是分析一组受NAFLD影响的个体和匹配的健康对照者中 Krebs 循环中间体的循环水平，并将我们的发现与肝功能指标相关联。对NAFLD组（n = 22）和匹配的对照组（n = 67）进行了标准血清生化和 Krebs 循环中间体分析。NAFLD患者队列中异柠檬酸和柠檬酸的循环水平显著升高（P < 0.05）。这两种代谢物的曲线下面积（AUROC）显示出中等的临床实用性。通过Pearson相关系数探讨血浆Krebs循环中间体与标准临床血浆指标之间的相关性。血浆Krebs循环中间体获得的数据提示了将线粒体功能障碍与NAFLD联系起来的病理生理学见解。我们的研究结果表明，血浆异柠檬酸和柠檬酸可以区分正常人群和NAFLD人群，并可作为NAFLD中线粒体功能障碍的非侵入性标志物。有必要对处于不同NAFLD阶段的大量人群进行进一步研究。
