| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 104 === Abstract
MicroRNA-122 is a liver-specific mircoRNA which plays an important role in lipid metabolism. In our previous study, Mir122a-/- mice of three month old displays fatty liver disease. Metformin, an anti-diabetic drug, controls blood glucose based mainly on activation of AMPK and subsequently inhibits glucose production in liver. Interestingly, it has been reported that metformin could rescue fatty liver disease in ob/ob mice. Therefore, we aimed to investigate whether metformin could improve fatty liver disease in Mir122a-/- mice. To elucidate whether miR-122 may play a role in regulating AMPK pathway, a hepatoma cell line, HuH7, was used for in vitro studies. We found that oleic acid induced lipid uptake and accumulation in HuH7 cells but significantly decreased lipid accumulation in the presence of metformin. Ectopic expression of hsa-miR-122 in HuH7 or Hep3B increased EGFR protein level suggesting that miR-122 may lead to activate AMPK through EGFR downstream pathways. Notably, Mir122a-/- mice exhibited declined AMPK activation and reduced EGFR expression in liver. To investigate the therapeutic role of metformin in fatty liver disease, Mir122a-/- mice were received metformin 250 mg/ kg for 6 weeks through gavage. Our preliminary data shows that neither reduced the accumulation of lipid droplets in hepatocytes, nor ameliorated the progression of fatty liver disease and liver fibrosis were found in Mir122a-/- mice. Taken these results together, metformin inhibits lipid accumulation in HuH7 cells. Yet, whether it may improve the progression of fatty liver disease in Mir122a-/- mice remains to be determined.
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