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The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice.
Life Sci. 2008 May 07; 82(19-20):983-90.LS

Abstract

Non-alcoholic steatohepatitis (NASH) is a hepatic manifestation of the metabolic syndrome that can progress to liver cirrhosis. The major aim of this study was to establish a novel NASH mouse model accompanied by obesity and insulin resistance, then explore the molecular mechanisms of NASH and evaluate the effects of both the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist fenofibrate and the PPARgamma agonist rosiglitazone in this established NASH model. The novel model was induced in C57BL/6 mice by 23 weeks of ad libitum feeding of a modified high-fat diet (mHFD), with lower methinione and choline and higher fat content. In comparison to the controls, the model animals developed pronounced obesity, dyslipidemia and insulin resistance. Marked liver lesions characterized by severe steatosis, inflammation, fibrosis, increased hepatic triglyceride content, and elevated serum alanine aminotransferase (ALT) levels were observed in the models. In this novel model, treatment with fenofibrate or rosiglitazone significantly improved insulin sensitivity and corrected dyslipidemia; however, fenofibrate was more effective than rosiglitazone in improving hepatic morphology and ALT levels. Further study showed that long-term feeding of mHFD significantly increased expression of mRNA for hepatic PPARgamma, adipose fatty acid binding protein (ap2) and CD36 and suppressed expression of mRNA for hepatic PPARalpha and carnitine palmitoyl transferase-1a (CPT-1a). These results showed the successful establishment of the combined NASH and obese-insulin resistance mouse model. Additionally, aberrant expressions of hepatic PPARalpha and PPARgamma may play a major role in the pathogenesis of NASH by affecting hepatic lipogenesis and fatty acid oxidation in this novel model.

Authors+Show Affiliations

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18417155

Citation

Cong, Wei-Na, et al. "The Establishment of a Novel Non-alcoholic Steatohepatitis Model Accompanied With Obesity and Insulin Resistance in Mice." Life Sciences, vol. 82, no. 19-20, 2008, pp. 983-90.
Cong WN, Tao RY, Tian JY, et al. The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sci. 2008;82(19-20):983-90.
Cong, W. N., Tao, R. Y., Tian, J. Y., Liu, G. T., & Ye, F. (2008). The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sciences, 82(19-20), 983-90. https://doi.org/10.1016/j.lfs.2008.01.022
Cong WN, et al. The Establishment of a Novel Non-alcoholic Steatohepatitis Model Accompanied With Obesity and Insulin Resistance in Mice. Life Sci. 2008 May 7;82(19-20):983-90. PubMed PMID: 18417155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. AU - Cong,Wei-Na, AU - Tao,Rong-Ya, AU - Tian,Jin-Ying, AU - Liu,Geng-Tao, AU - Ye,Fei, Y1 - 2008/03/04/ PY - 2007/09/22/received PY - 2008/01/23/revised PY - 2008/01/26/accepted PY - 2008/4/18/pubmed PY - 2008/7/11/medline PY - 2008/4/18/entrez SP - 983 EP - 90 JF - Life sciences JO - Life Sci VL - 82 IS - 19-20 N2 - Non-alcoholic steatohepatitis (NASH) is a hepatic manifestation of the metabolic syndrome that can progress to liver cirrhosis. The major aim of this study was to establish a novel NASH mouse model accompanied by obesity and insulin resistance, then explore the molecular mechanisms of NASH and evaluate the effects of both the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist fenofibrate and the PPARgamma agonist rosiglitazone in this established NASH model. The novel model was induced in C57BL/6 mice by 23 weeks of ad libitum feeding of a modified high-fat diet (mHFD), with lower methinione and choline and higher fat content. In comparison to the controls, the model animals developed pronounced obesity, dyslipidemia and insulin resistance. Marked liver lesions characterized by severe steatosis, inflammation, fibrosis, increased hepatic triglyceride content, and elevated serum alanine aminotransferase (ALT) levels were observed in the models. In this novel model, treatment with fenofibrate or rosiglitazone significantly improved insulin sensitivity and corrected dyslipidemia; however, fenofibrate was more effective than rosiglitazone in improving hepatic morphology and ALT levels. Further study showed that long-term feeding of mHFD significantly increased expression of mRNA for hepatic PPARgamma, adipose fatty acid binding protein (ap2) and CD36 and suppressed expression of mRNA for hepatic PPARalpha and carnitine palmitoyl transferase-1a (CPT-1a). These results showed the successful establishment of the combined NASH and obese-insulin resistance mouse model. Additionally, aberrant expressions of hepatic PPARalpha and PPARgamma may play a major role in the pathogenesis of NASH by affecting hepatic lipogenesis and fatty acid oxidation in this novel model. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/18417155/The_establishment_of_a_novel_non_alcoholic_steatohepatitis_model_accompanied_with_obesity_and_insulin_resistance_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(08)00088-X DB - PRIME DP - Unbound Medicine ER -