title: Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.
abstract: BACKGROUND
  Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart.
  
  
  METHODS
  Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens.
  
  
  RESULTS
  HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I.
  
  
  CONCLUSIONS
  These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Liaoliao
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D053148:Caspase 3 / Q000378:metabolism; D059305:Diet, High-Fat; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009206:Myocardium / Q000473:pathology*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3
keywords: Glycogen synthase kinase-3β; High fat diet; Intermittent fasting; Mice; Myocardial hypertrophy