title: High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy.
abstract: OBJECTIVE
  Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress.
  
  
  RESULTS
  HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 μM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress.
  
  
  CONCLUSIONS
  HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan.
authors.forename: Hsiu-Ching
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 112, 10673, Taiwan. ronichen@ntu.edu.tw.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan.
authors.forename: Bai-Chin
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000473:pathology*; D009765:Obesity / Q000473:pathology; D010168:Palmitates / Q000009:adverse effects; D051381:Rats; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D010168:Palmitates; D014280:Triglycerides; D002784:Cholesterol
keywords: Apoptosis; Autophagy; Cardiac hypertrophy; High-fat diet; Palmitate