Effects of Nuclear Factor Erythroid 2-Like 2 Deficiency on the Liver of High Fat Diet Induced Nonalcoholic Fatty Liver Disease Mouse Model

CUI Yizhe, WANG Qiuju, ZHANG Xiuying, WANG Chunhua, LI Guangliang, QI Yue

doi:10.3969/j.issn.1006-267x.2015.04.038

2015 , Vol. 27 >Issue 4: 1310 - 1315

DOI: https://doi.org/10.3969/j.issn.1006-267x.2015.04.038

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Effects of Nuclear Factor Erythroid 2-Like 2 Deficiency on the Liver of High Fat Diet Induced Nonalcoholic Fatty Liver Disease Mouse Model

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1. College of Veterinary Medicine, Northeast Agriculture University, Harbin 150030, China;
2. College of Animal Science and Veterinary, Heilongjiang Bayi Agricultural University, Daqing 163319, China

Received date: 2014-10-02

Online published: 2015-04-21

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Abstract

This experiment was conducted to study the effect of nuclear factor erythroid 2-like 2 (Nrf2) disruption on the development of oxidative stress of the mouse liver induced by high fat diet. Twenty male wild-type (WT) and twenty Nrf2 knockout (KO) mice on ICR background were randomly divided into two groups with ten mice in each group, respectively. Mice in the control group were fed the normal diet (ND), and the others were fed the high fat diet (HFD). The experiment lasted for 8 weeks.The results showed as follows: 1) compared with the control group mice, the total cholesterol (TC), low-density lipoprotein (LDL) content and alanine aminot ransferase (ALT), aspartat eaminotransferase (AST) activity of WT and KO mice in HFD group were significantly increased (P<0.01), the alkaline phosphatase (ALP) activity was significantly increased (P<0.05 or P<0.01), the total protein (TP) content was significantly decreased (P<0.01), but the triglycerides (TG) and high-density lipoprotein (HDL) content did not significantly changed (P>0.05). 2) Under the light microscope showed that WT high fat mice liver showed microvesicular steatosis, KO high fat mice liver showed gentle microvesicular steatosis and severe macrovesicular steatosis. 3) Compared with the control group, the glutathione (GSH) content and superoxide dismutase (SOD) activity of WT and KO mice in HFD group were significantly decreased (P<0.05 or P<0.01), while peroxidase (POD) activity and malondialdehyde (MDA) content were increased significantly (P<0.05 or P<0.01). Compared with the WT mice, the MDA content of KO mice in HFD group was increased 49%, but the GSH content and SOD, POD activity did not significantly changed (P>0.05). Compared with the WT mice in control group, the SOD, POD activity and MDA content of KO mice in HFD group were increased significantly (P<0.05 or P<0.01), while the GSH content was significantly decreased (P<0.01). The results indicated that Nrf2 deficient mice develope severe steatosis induced by high fat diet, and also high fat diet induces oxidative stress of nonalcoholic fatty liver disease mice.

Key words： high fat diet; fatty liver; oxidative stress; Nrf2; gene disruption

Cite this article

CUI Yizhe, WANG Qiuju, ZHANG Xiuying, WANG Chunhua, LI Guangliang, QI Yue . Effects of Nuclear Factor Erythroid 2-Like 2 Deficiency on the Liver of High Fat Diet Induced Nonalcoholic Fatty Liver Disease Mouse Model[J]. Chinese Journal of Animal Nutrition, 2015 , 27(4) : 1310 -1315 . DOI: 10.3969/j.issn.1006-267x.2015.04.038

References

[1] MACHADO M V, CORTEZ-PINTO H.Non-alcoholic fatty liver disease:what the clinician needs to know[J].World Journal of Gastroenterology, 2014, 20(36):12956-12980.

[2] 王明琼, 杨立军, 李盼盼, 等.奶牛脂肪肝临床诊断指标的筛选[J].中国兽医杂志, 2014, 50(5):43-45.

[3] 赵芹, 张海军, 武书庚, 等.吡咯喹啉醌对脂肪肝蛋鸡肝损伤的保护作用机制[J].动物营养学报, 2014, 26(3):651-658.

[4] 姜锦鹏, 宁康健, 吕锦芳, 等.实验性鸡脂肪肝出血综合征模型的建立与评价[J].中国实验动物学报, 2012, 20(3):69-73.

[5] CHOWDHRY S, NAZMY M H, MEAKIN P J, et al.Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis[J].Free Radical Biology and Medicine, 2010, 48:357-371.

[6] TANG W, JIANG Y F, PONNUSAMY M, et al.Role of Nrf2 in chronic liver disease[J].World Journal of Gastroenterology, 2014, 20(36):13079-13087.

[7] 李晓冲, 徐尚, 张秀英, 等.C57BL6J小鼠非酒精性脂肪肝模型的建立[J].中国兽医杂志, 2013, 49(1):6-8.

[8] 中华肝病学会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].中华肝脏病杂志, 2010, 18(3):163-166.

[9] MOFRAD P, CONTOS M J, HAQUE M, et al.Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values [J].Hepatology, 2003, 6(37):1286-1292.

[10] 邵洛林, 许伟华, 周成军, 等.Nrf2在小鼠非酒精性脂肪性肝病发病机制中的作用[J].山东大学学报, 2010, 48(3):53-46.

[11] TANAKA Y, ALEKSUNES L M, YEAGER R L, et al.NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet[J].The Journal of Pharmacology and Experimental Therapeutics, 2008, 325 (2):655-664.

[12] KIM S, SOHN I, AHN J I, et al.Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model[J].Gene, 2004, 340 (1):99-109.

[13] PASTORE A, FEDERICI G, BERTINI E, et al.Analysis of glutathione:implication in redox and detoxification[J].Clinica Chimica Acta, 2003, 333:19-39.

[14] ZOU Y, LI J, LU C, et al.High-fat emulsion-induced rat model of nonalcoholic steatohepatiis[J].Life Science, 2006, 79:1100-1107.

[15] SARICAM T, KIRCALI B, KOKEN T.Assessment of lipid peroxidation and antioxidant capacity in non-alcoholic fatty liver disease[J].Turkish Journal of Gastroenterology, 2005, 16:65-70.

[16] VIDELA LA, RODRIGO R, ORELLANA M, et al.Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients[J].Clinical Science, 2004, 106:261-268.

[17] KORUK M, TAYSI S, SAVA S MC, et al.Oxidative stress and enzymatic antioxidant status in Patients with nonalcoholic steatohepatiis[J].Annals of Clinical and Laboratory Science, 2004, 34:57-62.

[18] BHARDWAJ P, MADAN K, THAREJA S, et al.Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease[J].Hepatology International, 2008, 2:202-208.

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