A nutritional nonalcoholic steatohepatitis minipig model

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• 作者：Sin-Jin Li^a ; Shih-Torng Ding^a ; Harry J. Mersmann^a ; Chun-Han Chu^a ; Chia-Da Hsu^b ; Ching-Yi Chen^a ; ^{ronichen@ntu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：T2DM ; type 2 diabetes mellitus ; CVD ; cardiovascular disease ; NAFLD ; nonalcoholic fatty liver disease ; NASH ; nonalcoholic steatohepatitis ; HSCs ; hepatic stellate cells ; ER ; endoplasmic reticulum ; UPR ; unfolded protein response ; MCD ; methionine- and choline-deficient ; HFD ; high-fat diet ; GRP94 ; glucose-regulated protein of 94 kDa ; CHOP ; C/EBP homologous protein ; LC3 ; microtubule-associated protein 1A/1B-light chain 3 ; BNIP3 ; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 ; PARP ; poly(ADP-
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：28
• 期：Complete
• 页码：51-60
• 全文大小：1757 K

文摘

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.

3">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.