Auguet Teresa, Aragonès Gemma, Berlanga Alba, Guiu-Jurado Esther, Martí Andreu, Martínez Salomé, Sabench Fàtima, Hernández Mercé, Aguilar Carmen, Sirvent Joan Josep, Del Castillo Daniel, Richart Cristóbal
Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Tarragona 43007, Spain.
Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain.
Int J Mol Sci. 2016 Sep 24;17(10):1620. doi: 10.3390/ijms17101620.
Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.
特定的微小RNA（miRNA）表达谱已被证明与非酒精性脂肪性肝病（NAFLD）相关。我们研究了miR122和miR33a/b的循环水平与肝脏表达之间的相关性，以及关键脂质代谢相关基因的表达和肥胖NAFLD女性的临床病理因素。我们测量了62例病态肥胖（MO）、30例中度肥胖（ModO）和8例正常体重对照者肝脏样本中miR122和miR33a/b的表达。通过qRT-PCR分析miR122和miR33a/b的表达。此外，还分析了122名女性中miR122和miR33b的循环水平。与ModO和对照组相比，MO组肝脏miR33b表达增加，而与ModO组相比，MO组miR122表达降低。在肥胖队列中，非酒精性脂肪性肝炎（NASH）患者的miR33b表达增加。关于循环水平，患有NASH的MO患者的miR122水平高于单纯性脂肪变性（SS）的MO患者。这些循环水平是与疾病严重程度相关的组织学特征的良好预测指标。MO与肝脏miRNA表达改变有关。在肥胖女性中，肝脏中较高的miR33b*表达与NASH相关。此外，还发现了miRNA与脂质代谢相关基因表达之间的多重相关性，这表明存在miRNA-宿主基因回路。最后，miR122循环水平可纳入一组不同的生物标志物中，以提高NASH无创诊断的准确性。
