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A novel non-alcoholic steatohepatitis animal model featured with insulin resistance, hepatic inflammation and fibrosis.

Authors: Zhao, J  Zhou, G  Li, M  Li, W  Lu, J  Xiong, L  Liang, L  Zhao, Y  Xu, D  Yu, J 
Citation: Zhao J, etal., Scand J Gastroenterol. 2010 Nov;45(11):1360-71. doi: 10.3109/00365521.2010.497938. Epub 2010 Jun 21.
Pubmed: (View Article at PubMed) PMID:20560816
DOI: Full-text: DOI:10.3109/00365521.2010.497938

OBJECTIVE: There is no animal model that displays the features of non-alcoholic steatohepatitis (NASH) characterized by insulin resistance (IR) and fibrosing steatohepatitis. This study aimed to develop a novel IR-associated rat model of NASH. MATERIAL AND METHODS: Male Sprague-Dawley rats were fed with the high-fat diet (HFD) supplemented with 0.25% propylthiouracil for 2, 4, 6, 8 and 12 weeks. The IR-associated metabolic parameters, histological assessment and the expression of key insulin signaling molecules were determined. The circulating and tissue pro-inflammatory factors and adipocytokines were examined. RESULTS: In the HFD-fed rats, the systemic and multiple-organ IR was developed after 4 weeks, whereas the histological changes characterized by steatohepatitis, inflammatory response in the visceral adipose tissue and proliferative pancreatic islet beta-cells appeared after 6 weeks, concomitant with altered expression of key insulin signaling molecules. In addition, the elevated levels of serum tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor2, interleukin (IL)-6, CC-chemokine ligand (CCL)2 and resistin were parallel with the severity of hepatic inflammation, while the levels of serum adiponectin, leptin and TNF-alpha, but not resistin, were correlated with IR. CONCLUSIONS: We have developed a systemic IR-associated NASH model of rats, with impaired insulin signaling, systemic inflammation and appropriate pathology characterized by human NASH, and provided a realistic experimental model for elucidating the association between IR and the pathogenesis of NASH.

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RGD Object Information
RGD ID: 7207249
Created: 2013-01-25
Species: All species
Last Modified: 2013-01-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.