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J Nutr Biochem. 2016 Feb;28:51-60. doi: 10.1016/j.jnutbio.2015.09.029. Epub 2015 Oct 26.

A nutritional nonalcoholic steatohepatitis minipig model.

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Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
School of Veterinary Medicine, National Taiwan University, No. 1, Sec 4, Roosevelt Rd, Taipei 106, Taiwan.
Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan. Electronic address:



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.


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.


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.


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.


Autophagy; ER stress; IL-6; Lee–Sung minipigs; NAFLD; SAA

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