A nutritional nonalcoholic steatohepatitis minipig model
Journal
Journal of Nutritional Biochemistry
Journal Volume
28
Pages
51-60
Date Issued
2016
Author(s)
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. ? 2015 Elsevier Inc.
Subjects
Autophagy; ER stress; IL-6; Lee-Sung minipigs; NAFLD; SAA
SDGs
Other Subjects
collagen; fatty acid; glucose regulated protein 94; insulin; interleukin 1; interleukin 6; macrophage activating factor; macrophage stimulating protein alpha; osteoprotegerin; plasminogen activator inhibitor; platelet derived growth factor AA; receptor; resistin; serum amyloid A; somatomedin C; thiobarbituric acid reactive substance; tumor necrosis factor alpha; unclassified drug; vasculotropin; x linked ectodermal dysplasia receptor; animal experiment; animal model; animal tissue; antioxidant activity; Article; atherosclerosis; autophagy; body composition; body fat; controlled study; diet induced obesity; endoplasmic reticulum stress; fatty acid blood level; glucose intolerance; inflammation; insulin blood level; insulin resistance; lean body weight; liver fibrosis; minipig; non insulin dependent diabetes mellitus; nonalcoholic fatty liver; nonhuman; oxidative stress; porcine model; protein blood level; protein expression; regulatory mechanism; Western diet; animal; disease model; endoplasmic reticulum stress; minipig; nonalcoholic fatty liver; pathology; pig; Animals; Body Composition; Disease Models, Animal; Endoplasmic Reticulum Stress; Non-alcoholic Fatty Liver Disease; Swine; Swine, Miniature
Type
journal article