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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.

Author information

1
Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan.
2
School of Veterinary Medicine, National Taiwan University, No. 1, Sec 4, Roosevelt Rd, Taipei 106, Taiwan.
3
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.

Abstract

BACKGROUND AND AIMS:

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.

KEYWORDS:

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

PMID:
26878782
DOI:
10.1016/j.jnutbio.2015.09.029
[Indexed for MEDLINE]

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