PDF(Pubmed)
Abstract：
Background: Although the exact mechanisms of nonalcoholic fatty liver disease (NAFLD) are not fully understood, numerous pieces of evidence show that the variations in mitochondrial DNA (mtDNA) level and hepatic Fibroblast growth factor 21 (FGF21) expression may be related to NAFLD susceptibility. Objectives: The main objective of this study was to determine relative levels of mtDNA copy number and hepatic FGF21 expression in a cohort of Iranian NAFLD patients and evaluate the possible relationship. Methods: This study included 27 NAFLD patients (10 with nonalcoholic fatty liver (NAFL) and 17 with non-alcoholic steatohepatitis (NASH)) and ten healthy subjects. Total RNA and genomic DNA were extracted from liver tissue samples, and then mtDNA copy number and FGF21 expression levels were assessed by quantitative real-time PCR. Results: The relative level of hepatic mtDNA copy number was 3.9-fold higher in patients than in controls (p < 0.0001). NAFLD patients showed a 2.9-fold increase in hepatic FGF21 expression compared to controls (p < 0.013). Results showed that hepatic FGF21 expression was positively correlated with BMI, serum ALT, and AST levels (p < 0.05). The level of mitochondrial copy number and hepatic FGF21 expression was not significantly associated with stages of change in hepatic steatosis. Finally, there was a significant correlation between FGF21 expression and mitochondrial copy number in NAFLD patients (p = 0.027). Conclusion: Our findings suggest a considerable rise of hepatic FGF21 mRNA levels and mtDNA-CN and show a positive correlation between them in the liver tissue of NAFLD patients.
摘要：
背景：虽然非酒精性脂肪性肝病（NAFLD）的确切机制尚未完全了解，大量证据表明，线粒体DNA（mtDNA）水平和肝脏成纤维细胞生长因子21（FGF21）表达的变化可能与NAFLD易感性有关。目标：这项研究的主要目的是确定伊朗NAFLD患者队列中mtDNA拷贝数和肝脏FGF21表达的相对水平，并评估可能的关系。方法：这项研究包括27例NAFLD患者（10例非酒精性脂肪肝（NAFL）和17例非酒精性脂肪性肝炎（NASH））和10例健康受试者。从肝组织样本中提取总RNA和基因组DNA，然后通过定量实时PCR评估mtDNA拷贝数和FGF21表达水平。结果：患者肝脏mtDNA拷贝数的相对水平比对照组高3.9倍（p<0.0001）。与对照相比,NAFLD患者显示肝脏FGF21表达增加2.9倍(p<0.013)。结果显示肝脏FGF21表达与BMI呈正相关,血清ALT,和AST水平(p<0.05)。线粒体拷贝数和肝脏FGF21表达的水平与肝脏脂肪变性的变化阶段没有显着相关。最后,NAFLD患者FGF21表达与线粒体拷贝数之间存在显著相关性(p=0.027)。结论：我们的发现表明NAFLD患者肝组织中肝脏FGF21mRNA水平和mtDNA-CN的显着升高，并且它们之间呈正相关。
