马运芹, 陆俊茜, 郭凯锋, 赵芳雅, 潘盼, 徐振兴, 贾伟平, 陈海冰. 5-氨基乙酰丙酸对内质网应激水平及肥胖小鼠糖代谢的影响[J]. 环境与职业医学, 2015, 32(6): 589-592. DOI: 10.13213/j.cnki.jeom.2015.14652
引用本文: 马运芹, 陆俊茜, 郭凯锋, 赵芳雅, 潘盼, 徐振兴, 贾伟平, 陈海冰. 5-氨基乙酰丙酸对内质网应激水平及肥胖小鼠糖代谢的影响[J]. 环境与职业医学, 2015, 32(6): 589-592. DOI: 10.13213/j.cnki.jeom.2015.14652
MA Yun-qin , LU Jun-xi , GUO Kai-feng , ZHAO Fang-ya , PAN Pan , XU ZHEN-xing , JIA Wei-ping , CHEN Hai-bing . Effects of 5-Amino Levulinic Acid on Endoplasmic Reticulum Stress and Glucose Metabolism in Obese Mice[J]. Journal of Environmental and Occupational Medicine, 2015, 32(6): 589-592. DOI: 10.13213/j.cnki.jeom.2015.14652
Citation: MA Yun-qin , LU Jun-xi , GUO Kai-feng , ZHAO Fang-ya , PAN Pan , XU ZHEN-xing , JIA Wei-ping , CHEN Hai-bing . Effects of 5-Amino Levulinic Acid on Endoplasmic Reticulum Stress and Glucose Metabolism in Obese Mice[J]. Journal of Environmental and Occupational Medicine, 2015, 32(6): 589-592. DOI: 10.13213/j.cnki.jeom.2015.14652

5-氨基乙酰丙酸对内质网应激水平及肥胖小鼠糖代谢的影响

Effects of 5-Amino Levulinic Acid on Endoplasmic Reticulum Stress and Glucose Metabolism in Obese Mice

  • 摘要: 目的 探讨5-氨基乙酰丙酸(5-ALA)对内质网应激水平及肥胖小鼠糖代谢的影响及相关分子机制。

    方法 将10只8周龄C57BL/6J小鼠适应性喂养1周后,高脂饲料喂养16周诱导造模肥胖小鼠,将肥胖小鼠随机分为5-ALA处理组5-ALA灌胃5 mg/(kg& #183;d)和对照组磷酸盐缓冲液(PBS)灌胃1 mL/(kg& #183;d),连续9周,期间每周于空腹12 h后尾静脉取血检测小鼠的空腹血糖。9周后分离小鼠的肝脏和附睾脂肪组织提取RNA和蛋白,检测小鼠肝脏和脂肪组织中内质网应激相关基因C/EBP同源蛋白(CHOP)、X-盒结合蛋白1s(XBP-1s)、重链结合蛋白(BiP)、内质网Dnaj同系物4(ERdj4)的表达水平。

    结果 5-ALA处理小鼠空腹血糖于第5周(6.40& #177;0.35)mmol/L开始下降,波动变小,第7周5-ALA处理组空腹血糖水平(6.02& #177;0.17)mmol/L低于对照组(6.54& #177;0.05)mmol/L(P < 0.05)。实时聚合酶链反应(real-timePCR)结果显示,5-ALA可抑制由于肥胖导致的脂肪组织中XBP-1s的高表达(5-ALA处理组2-△△CT为0.029& #177;0.017,对照组为0.029& #177;0.006),P < 0.05;western blotting结果亦显示5-ALA处理组小鼠XBP-1s水平低于对照组。

    结论 5-ALA可能通过抑制白色脂肪组织中内质网应激通路IRE1-XBP-1通路缓解内质网应激水平,改善小鼠的血糖代谢。

     

    Abstract: Objective To examine the relationship of 5-amino levulinic acid (5-ALA) with endoplasmic reticulum stress and glucose metabolism and potential related molecular mechanisms.

    Methods Ten C57BL/6J mice at eight weeks of age were induced to establish obese mice model by 16-week high fat diet after one week of adaptive feeding, then randomly divided into an 5-ALA group5 mg/(kg& #183;d) and a control groupphosphate buffered saline 1 mL/(kg& #183;d), for nine consecutive weeks. During the intragastric administration, blood samples were collected from tail vein after 12 h of fasting for measuring fasting blood glucose levels. Nine weeks later, the mice liver and epididymal adipose tissues were separated to extract RNA and protein and measure the expressions of C/EBP homologous protein (CHOP), X-box binding protein 1s (XBP-1s), binding immunoglobulin protein (BiP), and endoplasmic reticulum DnaJ protein family member 4 (ERdj4).

    Results Compared with the control group(6.54& #177;0.05)mmol/L, the fasting blood glucose levels in the mice treated with 5-ALA were lowered from week 5(6.40& #177;0.35) mmol/L with little variation and showed a significant decrease at week 7(6.02& #177;0.17) mmol/L (P < 0.05). The real-time polymerase chain reaction results showed that 5-ALA significantly inhibited the increased mRNA levels of XBP-1s induced by obesity (2-△△CT for the 5-ALA group was 0.029& #177;0.017, 2-△△CT for the control group was 0.029& #177;0.006, P < 0.05). The western blotting results indicated that the expression of XBP-1s was lower in the 5-ALA group than in the control group.

    Conclusion 5-ALA could improve glucose metabolism in mice by inhibiting endoplasmic reticulum stress via IRE1-XBP-1 pathway in white adipose tissues.

     

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