Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia


  • S.M. Lee
  • D. Nguyen
  • M. Anand
  • R. Kant
  • C. Koehncke
  • U. Lisewski
  • T.K. Roepke
  • Z. Hu
  • G.W. Abbott


  • Scientific Reports


  • Sci Rep 6: 23118


  • Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel {beta} subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2(-/-) mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis.