miR33a/miR33b and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

• Published in: International journal of molecular sciences 2016-10, Vol.17 (10), p.1620
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; ATP Binding Cassette Transporter, Sub-Family G, Member 1 - genetics; ATP Binding Cassette Transporter, Sub-Family G, Member 1 - metabolism; Biomarkers - metabolism; Body Mass Index; Female; Gene expression; Humans; Lipid Metabolism - genetics; Liver - metabolism; Liver - pathology; Liver diseases; Logistic Models; Metabolic syndrome; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR122; miR33a/b; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - pathology; nonalcoholic fatty liver disease; Obesity; Obesity - complications; Obesity - genetics; Obesity - pathology; Severity of Illness Index; Sterol Regulatory Element Binding Protein 2 - genetics; Sterol Regulatory Element Binding Protein 2 - metabolism; Women
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.