A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism

Citations Over TimeTop 10% of 2015 papers

Abstract

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 4α (HNF4α), 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 HNF4α 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 HNF4α-dependent manner. As a result, increased miR-34a or reduced HNF4α expression in the liver attenuates the development of atherosclerosis in Apoe(-/-) or Ldlr(-/-) mice. These data indicate that the miR-34a-HNF4α 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.

Related Papers

• → Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease(2008)250 cited
• → Are Steatosis and Steatohepatitis Triggers of Hepatic Fibrogenesis(2013)2 cited
• → 1232 XANTHOHUMOL IMPROVES GLUCOSE TOLERANCE AND INHIBITS HEPATIC STEATOSIS, INFLAMMATION AND FIBROGENESIS IN A MURINE MODEL OF NON-ALCOHOLIC STEATOHEPATITIS(2012)
• → Faculty Opinions recommendation of Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis.(2008)
• → STUDY OF CELL MODELS OF HEPG2 STEATOSIS AND STEATOHEPATITIS VIABILITY(2023)