肝脏ChREBP在有氧运动预防C57BL/6小鼠非酒精性脂肪肝形成中的作用

doi:10.13418/j.issn.1001-165x.2014.04.018

中国临床解剖学杂志 ›› 2014, Vol. 32 ›› Issue (4): 446-450.doi: 10.13418/j.issn.1001-165x.2014.04.018

肝脏ChREBP在有氧运动预防C57BL/6小鼠非酒精性脂肪肝形成中的作用

吴皓¹，刘畅¹，管又飞²，　王春炅²，　李沙²

1.辽宁医学院附属第一医院内分泌病科, 辽宁锦州 121001；　2北京大学医学部基础医学院
生理学与病理生理学系, 北京 100191

收稿日期:2013-12-10 出版日期:2014-07-25 发布日期:2014-08-07
通讯作者: 刘畅，教授， E-mail: liuchang1971mei@163.com E-mail:wuhao19870205@163.com
作者简介:吴皓（1987-），男，浙江温州人，研究方向：内分泌与代谢病的研究，Tel:15940633010
基金资助:
国家自然科学基金（31100858）；辽宁省科技厅攻关技术项目（2012225019）

The effect of liver ChREBP on aerobic exercise preventing HFD-induced NAFLD in C57BL/6 mice

WU Hao¹, LIU Chang¹, GUAN You-fei², WANG Chun-jiong²，LI Sha²

1. Department of Endocrinology, First Affiliated Hospital, Liaoning Medical University, Jinzhou 121001, China; 2. Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China

Received:2013-12-10 Online:2014-07-25 Published:2014-08-07

摘要/Abstract

摘要：

目的　探讨肝脏碳水化合物反应元件结合蛋白（ChREBP）基因及其下游靶基因在12周有氧运动预防C57BL/6小鼠非酒精性脂肪肝（NAFLD）中的作用。方法　8周龄C57BL/6小鼠随机分为正常饮食组（ND），正常饮食运动组（ND-Ex），高脂饮食组（HFD），高脂饮食运动组（HFD-Ex）。高脂喂养进行非酒精性脂肪肝造模。有氧运动采用无负重游泳。检测各组小鼠肝脏、血甘油三脂及总胆固醇含量，空腹血糖，口服糖耐量，肝中脂质沉积情况，肝脏ChREBP基因及其下游靶基因表达变化，肝脏Akt磷酸化水平。结果　与ND组相比，HFD组小鼠体重及血脂增加，肝甘油三酯增加并出现明显脂质沉积，血糖调节能力下降，ChREBP基因及其下游靶基因表达增加，Akt磷酸化水平下降。与HFD组相比，HFD-Ex组小鼠血脂下降，肝甘油三酯含量减少、脂质沉积减轻，未出现空腹血糖及糖耐量异常，ChREBP基因及其下游靶基因表达下降，Akt磷酸化水平增加。结论　有氧运动对高脂饮食诱导的非酒精性脂肪肝有预防作用，这可能与有氧运动抑制ChREBP基因表达有关。

关键词: 有氧运动, 非酒精性脂肪肝, ChREBP, FAS, SCD1

Abstract:

Objective　To investigate the effect of ChREBP and its downstream target genes on 12-week aerobic exercise prevention C57BL/6 mice with nonalcoholic fatty liver.　Methods　Forty-two male C57BL/6 mice were randomized into four groups (n=8~13): the normal diet sedentary group (ND) (n=8), the normal diet exercised group (ND-Ex), the high-fat diet sedentary group (HFD) and the high-fat diet exercised group (HFD-Ex). After the simultaneous starting of high-fat diet feeding, the mice were submitted to an aerobic swimming training protocol (60 minutes/day) five days per week, for 12 weeks. At the end of the experiment, mice liver, blood triglycerides and total cholesterol, fasting blood glucose, oral glucose tolerance were determined. The expression of ChREBP and its downstream target genes were measured by RT-PCR. The level of Akt phosphorylation in liver was measured by Western blot.　Result　Compared with group ND, group HFD had significantly higher body weight, impaired oral glucose tolerance, dyslipidemia, liver steatosis and NAFLD. The expression of ChREBP and its downstream target genes in group HFD were significantly increased, and the level of Akt phosphorylation in liver was decreased. Compared with group HFD, aerobic exercise reduced overweight and all the other worst findings, especially NAFLD in group HFD-Ex. The expression of ChREBP and its downstream target genes in group HFD-Ex were decreased, and the level of Akt phosphorylation in liver was increased.　Conclusion　Aerobic exercise has a preventive effect on high-fat diet-induced NAFLD, and this may be related to aerobic exercise inhibition of ChREBP and its downstream target genes expression.

Key words: Aerobic exercise, non-alcoholic fatty liver disease, ChREBP, FAS, SCD1

中图分类号:

吴皓, 刘畅, 管又飞, 王春炅, 李沙. 肝脏ChREBP在有氧运动预防C57BL/6小鼠非酒精性脂肪肝形成中的作用[J]. 中国临床解剖学杂志, 2014, 32(4): 446-450.

TUN Hao, LIU Chang, GUAN You-Fei, WANG Chun-Gui, LI Sha. The effect of liver ChREBP on aerobic exercise preventing HFD-induced NAFLD in C57BL/6 mice[J]. Chinese Journal of Clinical Anatomy, 2014, 32(4): 446-450.

参考文献

[1] Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China
[J]. J Hepatol, 2009, 50(1): 204-210.

[2] Lidofsky SD. Nonalcoholic fatty liver disease: diagnosis and relation to metabolic syndrome and approach to treatment
[J]. Curr Diab Rep, 2008, 8(1): 25-30.

[3] Sourianarayanane A, Pagadala MR, Kirwan JP. Management of non-alcoholic fatty liver disease
[J]. Minerva Gastroenterol Dietol, 2013,59(1): 69-87.

[4] American College of Sports Medicine. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults
[J]. Med Sci Sports Exerc, 2009, 41(3): 687-708.

[5] Li J, Chi Y, Wang C, et al. Pancreatic-derived factor promotes lipogenesis in the mouse liver: role of the Forkhead box 1 signaling pathway
[J]. Hepatology, 2011, 53(6):1906-1916.

[6] Yang J, Wang C, Li J, et al. PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells
[J]. FEBS Lett, 2009, 583(18): 3009-3015.

[7] Day CP. Pathogenesis of steatohepatitis
[J]. Best Pract Res Clin Gastroenterol, 2002,16(5): 663-678.

[8] van der Heijden GJ, kWang ZJ, Chu ZD, et al. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents
[J]. Obesity (Silver Spring), 2010, 18(2): 384-390.

[9] Sullivan S,Kirk EP, Mittendorfer B, et al. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease
[J]. Hepatology, 2012, 55(6): 1738-1745.

[10]Iizuka K, Miller B, Uyeda K. Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice
[J]. Am J Physiol Endocrinol Metab, 2006, 291(2): E358-364.

[11]Dentin R, Benhamed F, Hainault I, et al. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice
[J]. Diabetes, 2006, 55(8): 2159-2170.

[12]Guinez, C., et al., O-GlcNAcylation increases ChREBP protein content and transcriptional activity in the liver
[J]. Diabetes, 2011, 60(5):1399-1413.

肝脏ChREBP在有氧运动预防C57BL/6小鼠非酒精性脂肪肝形成中的作用

The effect of liver ChREBP on aerobic exercise preventing HFD-induced NAFLD in C57BL/6 mice

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

Metrics

本文评价

推荐阅读 0

[1]	郑方芳，郭新铭，钟北龙，蒋小云. 香叶木素对非酒精性脂肪肝病幼鼠的保护作用[J]. 中国临床解剖学杂志, 2018, 36(5): 520-526.
[2]	徐年香, 刘曾旭, 罗小凤, 程华, 余庆, 刘卉芳, 刘德??. 自体嗅粘膜联合β-七叶皂甙钠对脊髓损伤后FasL及Caspase-3表达的影响[J]. 中国临床解剖学杂志, 2012, 30(2): 214-217.