title: A nutritional nonalcoholic steatohepatitis minipig model.
abstract: OBJECTIVE
  The objective of this study was to elucidate whether a Western diet was associated with nonalcoholic steatohepatitis (NASH), and the relationship between NASH, autophagy and endoplasmic reticulum (ER) stress.
  
  
  METHODS
  Four-month-old Lee-Sung minipigs were randomly assigned to two groups: control diet (C) and Western diet (W), for a 5-month experimental period.
  
  
  RESULTS
  Feeding a Western diet produced a body composition with more fat, less lean and a greater liver weight. Compared with C pigs, W pigs also exhibited an elevated level of plasma insulin and free fatty acid. The W pigs displayed glucose intolerance, lower circulation antioxidant capacity and greater hepatic oxidative stress. Furthermore, pig fed the W diets had increased collagen accumulation in the liver and elevated systemic inflammation [tumor necrosis factor α and interleukin (IL)-6]. Compared with C pigs, W pigs had higher hepatic ER stress-related protein expression of GRP94, CHOP and caspase-12. The W pigs also had greater hepatic autophagy-related protein expression of p62 and LC3II. In an obesity antibody array analysis, W pigs had higher type 2 diabetes mellitus- (insulin-like growth factor 1, osteoprotegerin and resistin), atherosclerosis- (vascular endothelial growth factor, platelet-derived growth factor-AA and plasminogen activator inhibitor-I) and inflammation- [IL-1, macrophage-stimulating protein alpha, X-linked ectodermal dysplasia receptor and serum amyloid A (SAA)] related protein expressions. In addition, W pigs had greater plasma SAA concentration than C pigs and plasma SAA level was highly associated with IL-6.
  
  
  CONCLUSIONS
  We successfully established a NASH pig model, and our findings suggested an association of NASH with ER stress and autophagy. The SAA has potential as a novel plasma biomarker for nonalcoholic fatty liver disease pigs.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
authors.forename: Sin-Jin
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Mersmann
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Chu
authors.affiliation: School of Veterinary Medicine, National Taiwan University, No. 1, Sec 4, Roosevelt Rd, Taipei 106, Taiwan.
authors.forename: Chia-Da
authors.initials: CD
authors.lastname: Hsu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan. Electronic address: ronichen@ntu.edu.tw.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001823:Body Composition; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature
keywords: Autophagy; ER stress; IL-6; Lee–Sung minipigs; NAFLD; SAA