RESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.
RESUMEN
OBJECTIVE: To investigate the correlation between Adiponectin gene polymorphisms and the genetic susceptibility of nonalcoholic fatty liver disease (NAFLD). METHODS: 357 NAFLD patients from January 2005 to December 2013 and 357 cases of healthy controls among the Han population were collected; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect three tagSNPs (Rs2241767, rsl501299 and rs3774261) of Adiponectin. Risk factors were analyzed by multivariate logistic regression and haplotype analysis was performed using SHEsis software. RESULTS: Rs2241767, rsl501299 and rs3774261 polymorphisms were associated with the risk of NAFLD. Haplotype analysis showed that, A-T-A haplotype was a protective factor of NAFLD (OR: 0.154, 95% CI: 0.011-0.576, P = 0.004) and G-G-A (OR: 4.012, 95% CI: 2.118-10.324, P < 0.001) and G-T-G (OR: 5.219, 95% CI: 2.751-12.651, P < 0.001) haplotype was risk factors of NAFLD. CONCLUSION: There was an association between Adiponectin gene polymorphisms and the genetic susceptibility of NAFLD.