| First Author | Xu Y | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7466 | PubMed ID | 26100857 |
| Mgi Jnum | J:223016 | Mgi Id | MGI:5646333 |
| Doi | 10.1038/ncomms8466 | Citation | Xu Y, et al. (2015) A metabolic stress-inducible miR-34a-HNF4alpha pathway regulates lipid and lipoprotein metabolism. Nat Commun 6:7466 |
| abstractText | Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, but its underlying mechanism is poorly understood. Here we show that hepatocyte nuclear factor 4alpha (HNF4alpha), a liver-enriched nuclear hormone receptor, is markedly inhibited, whereas miR-34a is highly induced in patients with non-alcoholic steatohepatitis, diabetic mice and mice fed a high-fat diet. miR-34a is essential for HNF4alpha expression and regulates triglyceride accumulation in human and murine hepatocytes. miR-34a inhibits very low-density lipoprotein secretion and promotes liver steatosis and hypolipidemia in an HNF4alpha-dependent manner. As a result, increased miR-34a or reduced HNF4alpha expression in the liver attenuates the development of atherosclerosis in Apoe(-/-) or Ldlr(-/-) mice. These data indicate that the miR-34a-HNF4alpha pathway is activated under common conditions of metabolic stress and may have a role in the pathogenesis of NAFLD and in regulating plasma lipoprotein metabolism. Targeting this pathway may represent a novel approach for the treatment of NAFLD. |
