title: Palmitate induces apoptosis in mouse aortic endothelial cells and endothelial dysfunction in mice fed high-calorie and high-cholesterol diets.
abstract: OBJECTIVE
  Obesity is associated with hypertriglyceridemia and elevated circulating free fatty acids (FFA), resulting in endothelial dysfunction. Endoplasmic reticulum (ER) stress has been implicated in many of these processes. To determine if ER stress participates in palmitate-induced apoptosis, we investigated the effects of diet-induced obesity and palmitate on mouse aortic endothelial cells (MAEC) in vivo and in vitro.
  
  
  METHODS
  Male C57BL/6 mice were fed standard chow diets (SCD) or high-calorie and high-cholesterol diets (HCD) for 3 months. Insulin resistance was detected, and the serum, including proinflammatory indices and markers of endothelial function, was also analyzed. The ultrastructure and apoptosis of the endothelial cells in the thoracic aorta were observed. The primary MAEC were separated and treated with palmitate at different concentrations or different times respectively to observe any changes in cellular proliferation, intracellular reactive oxygen species (ROS) levels and apoptosis. Finally, the ER stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were analyzed.
  
  
  RESULTS
  HCD-fed obese mice became inflammation-activated and insulin-resistant. Swollen mitochondria, expanded ER and apoptosis in the endothelial cells of the thoracic aorta were observed in HCD-fed mice. Palmitate inhibited cell proliferation, increased production of ROS and induced apoptosis in MAEC. CHOP was overexpressed and shifted into the nucleus (mainly), while the expression of GRP78 was upregulated in the palmitate-treated MAEC.
  
  
  CONCLUSIONS
  Our results indicate that diet-induced obesity results in endothelial dysfunction in vivo, and that oxidative and ER stress may be involved in apoptosis induced by the palmitate in vitro.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China. wwwdluyx@sina.com
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Qian
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Gui
authors.forename: Dake
authors.initials: D
authors.lastname: Huang
authors.forename: Guanjun
authors.initials: G
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000009:adverse effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002149:Energy Intake / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D019308:Palmitic Acid / Q000633:toxicity*; D011897:Random Allocation
chemical_list: D002791:Cholesterol, Dietary; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D019308:Palmitic Acid