Evaluation of Fbxw7 expression and its correlation with expression of SREBP-1 in a mouse model of NAFLD

Tu,Kangsheng; Zheng,Xin; Yin,Guozhi; Zan,Xianfeng; Yao,Yingmin; Liu,Qingguang

doi:10.3892/mmr.2012.953

September 2012 Volume 6 Issue 3

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September 2012 Volume 6 Issue 3

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Article

Evaluation of Fbxw7 expression and its correlation with expression of SREBP-1 in a mouse model of NAFLD

Authors:
- Kangsheng Tu
- Xin Zheng
- Guozhi Yin
- Xianfeng Zan
- Yingmin Yao
- Qingguang Liu
View Affiliations / Copyright

Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an 710061, P.R. China
Pages: 525-530
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Published online on: June 18, 2012

https://doi.org/10.3892/mmr.2012.953
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Abstract

The problems of aging, obesity and a number of types of metabolic syndromes, including diabetes, are associated with a higher risk of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms of occurrence and development of NAFLD in humans remain unclear. Sterol regulatory element binding protein (SREBP)-1 is a transcription factor that is important in the development of NAFLD, which regulates the expression of lipogenic genes. SREBP-1 might be degraded through an F-box and WD repeat domain‑containing 7 (Fbxw7)-dependent degradation. However, whether or not there is a correlation between Fbxw7 and SREBP-1 in NAFLD remains to be determined. The aim of this study was to investigate whether there was a reduction of Fbxw7 in NAFLD and an induced accumulation of SREBP-1 in a mouse model of NAFLD. Forty C57BL/6J mice were divided into control and HF groups and maintained on normal or high-fat (HF) diets. Following 8 weeks of treatment, the mice were sacrificed and assays of blood biomarkers typical of human NAFLD were performed. Liver samples were processed for histological examination. Fbxw7 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and the protein expression of Fbxw7 and SREBP-1 was evaluated by immunohistochemistry and western blot analysis in the mouse liver tissues in the control and HF groups. The mRNA and protein expression of Fbxw7 was significantly decreased in the HF group compared with the control group (P<0.05, for both). In the HF group, the Fbxw7 protein expression was negatively correlated with SREBP-1 (r=-0.584; P<0.05). Fbxw7 was decreased in NAFLD and negatively correlated with SREBP-1, indicating that the Fbxw7-SREBP-1 axis may play a key pathological role in the development of NAFLD.

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1	Hamaguchi E, Takamura T, Sakurai M, et al: Histological course of nonalcoholic fatty liver disease in Japanese patients: tight glycemic control, rather than weight reduction, ameliorates liver fibrosis. Diabetes Care. 33:284–286. 2010. View Article : Google Scholar
2	Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Järvinen H and Svegliati-Baroni G: From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 42:320–330. 2010. View Article : Google Scholar : PubMed/NCBI
3	Ogawa T, Fujii H, Yoshizato K and Kawada N: A human-type nonalcoholic steatohepatitis model with advanced fibrosis in rabbits. Am J Pathol. 177:153–165. 2010. View Article : Google Scholar : PubMed/NCBI
4	Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y and Uno M: Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology. 132:282–293. 2007. View Article : Google Scholar : PubMed/NCBI
5	Bugianesi E, Moscatiello S, Ciaravella MF and Marchesini G: Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des. 16:1941–1951. 2010. View Article : Google Scholar : PubMed/NCBI
6	Nakamuta M, Kohjima M, Morizono S, et al: Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med. 16:631–635. 2005.PubMed/NCBI
7	Foufelle F and Ferré P: New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J. 366:377–391. 2002. View Article : Google Scholar
8	Hagen RM, Rodriguez-Cuenca S and Vidal-Puig A: An allostatic control of membrane lipid composition by SREBP1. FEBS Lett. 584:2689–2698. 2010. View Article : Google Scholar : PubMed/NCBI
9	Nakayama H, Otabe S, Ueno T, et al: Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis. Metabolism. 56:470–475. 2007. View Article : Google Scholar
10	Sundqvist A, Bengoechea-Alonso MT, Ye X, et al: Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF^Fbw7. Cell Metab. 1:379–391. 2005. View Article : Google Scholar : PubMed/NCBI
11	Welcker M and Clurman BE: FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 8:83–93. 2008. View Article : Google Scholar : PubMed/NCBI
12	Kirpich IA, Gobejishvili LN, Bon Homme M, et al: Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet-induced nonalcoholic fatty liver disease. J Nutr Biochem. 22:38–45. 2011. View Article : Google Scholar : PubMed/NCBI
13	Onoyama I, Suzuki A, Matsumoto A, et al: Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J Clin Invest. 121:342–354. 2010. View Article : Google Scholar : PubMed/NCBI
14	Livnat-Levanon N and Glickman MH: Ubiquitin-proteasome system and mitochondria-reciprocity. Biochim Biophys Acta. 1809:80–87. 2011. View Article : Google Scholar
15	Chan NC, Salazar AM, Pham AH, et al: Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 20:1726–1737. 2011. View Article : Google Scholar : PubMed/NCBI
16	Willis MS, Townley-Tilson WH, Kang EY, Homeister JW and Patterson C: Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease. Circ Res. 106:463–478. 2010. View Article : Google Scholar : PubMed/NCBI
17	Bashir T and Pagano M: Aberrant ubiquitin-mediated proteolysis of cell cycle regulatory proteins and oncogenesis. Adv Cancer Res. 88:101–144. 2003.PubMed/NCBI
18	Sundaram M and Greenwald I: Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and glp-1 in Caenorhabditis elegans. Genetics. 135:765–783. 1993.PubMed/NCBI
19	Nash P, Tang X, Orlicky S, et al: Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature. 414:514–521. 2001. View Article : Google Scholar : PubMed/NCBI
20	Bengoechea-Alonso MT and Ericsson J: SREBP in signal transduction: cholesterol metabolism and beyond. Curr Opin Cell Biol. 19:215–222. 2007. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Evaluation of Fbxw7 expression and its correlation with expression of SREBP-1 in a mouse model of NAFLD

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