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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

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【作者】 吴皓刘畅管又飞王春炅李沙

【Author】 WU Hao;LIU Chang;GUAN You-fei;WANG Chun-jiong;LI Sha;Department of Endocrinology, First Affiliated Hospital, Liaoning Medical University;Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences;

【机构】 辽宁医学院附属第一医院内分泌病科北京大学医学部基础医学院生理学与病理生理学系

【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。

【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 HFDEx. 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.

【关键词】 有氧运动非酒精性脂肪肝ChREBPFASSCD1
【Key words】 Aerobic exercisenon-alcoholic fatty liver diseaseChREBPFASSCD1
【基金】 国家自然科学基金(31100858);辽宁省科技厅攻关技术项目(2012225019)
  • 【文献出处】 中国临床解剖学杂志 ,Chinese Journal of Clinical Anatomy , 编辑部邮箱 ,2014年04期
  • 【分类号】R575.5
  • 【被引频次】5
  • 【下载频次】302
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