摘要
目的:探究肠道菌群代谢产物短链脂肪酸对小鼠肝细胞AML12糖脂代谢的影响。方法:将AML12小鼠肝细胞分别在1、2、4、8和16 mmol/L浓度的乙酸钠、丙酸钠和丁酸钠中孵育24 h,Western印迹检测糖脂代谢信号通路中关键蛋白蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)、腺苷酸活化蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)的磷酸化水平以及AMPK总蛋白的表达量。结果:16 mmol/L丙酸钠显著升高Akt磷酸化水平,为对照组的(1.56±0.09)倍(F=3.251,P<0.05),丁酸钠在8 mmol/L时即可显著增加Akt的磷酸化,为对照组的(1.66±0.18)倍(F=8.249,P<0.05),而乙酸钠不影响Akt的磷酸化。8 mmol/L丁酸钠即可显著上调GSK-3β的磷酸化水平,为对照组的(1.61±0.14)倍(F=4.690,P<0.05),而乙酸钠和丙酸钠不影响GSK-3β的磷酸化。乙酸钠、丙酸钠和丁酸钠在不影响AMPK总蛋白表达的情况下,分别在2、1、2 mmol/L时即可显著升高AMPK磷酸化水平,分别为对照组的(1.40±0.13)倍(F=4.720,P<0.05)、(1.66±0.18)倍(F=16.54,P<0.05)和(1.70±0.13)倍(F=23.50,P<0.05)。乙酸钠、丙酸钠和丁酸钠分别在16、4、1 mmol/L即可显著升高ACC磷酸化水平,分别为对照组的(2.01±0.30)倍(F=4.807,P<0.01)、(1.66±0.18)倍(F=7.507,P<0.05)和(1.79±0.06)倍(F=7.028,P<0.01)。结论:短链脂肪酸可能通过调节肝细胞Akt/GSK-3β和AMPK/ACC通路减少肝脏脂质积聚并降低血糖。
Objective:To investigate the role of short chain fatty acids produced by intestinal flora on glucose and lipid metabolism in mouse AML12 hepatocytes.Methods:AML12 mouse hepatocytes were incubated in 1,2,4,8 and 16 mmol/L concentrations of sodium acetate,sodium propionate and sodium butyrate for 24 hours,respectively.The level of p-protein kinase B(Akt),p-glycogen synthase kinase-3β(GSK-3β),p-AMP activated protein kinase(AMPK),p-acetyl-CoA carboxylase(ACC)and expression of AMPK were determined by Western blotting.Results:16 mmol/L sodium propionate significantly increased the phosphorylation of Akt[(1.56±0.09)-fold vs.control group](F=3.251,P<0.05),8 mmol/L sodium butyrate significantly phosphorylated Akt[(1.66±0.18)-fold vs.control group](F=8.249,P<0.05),while sodium acetate did not affect the level of p-Akt.8 mmol/L sodium butyrate significantly increased the level of p-GSK-3β[(1.61±0.14)-fold vs.control group](F=4.690,P<0.05),while sodium acetate and sodium propionate did not affect p-GSK-3β.2 mmol/L sodium acetate,1 mmol/L sodium propionate and 2 mmol/L sodium butyrate significantly increased the phosphorylation of AMPK[(1.40±0.13)-fold,(1.66±0.18)-fold,(1.70±0.13)-fold vs.control group,respectively](all P<0.05;F=4.720,16.54,23.50)without affecting the expression of AMPK.16 mmol/L sodium acetate,4 mmol/L sodium propionate and 1 mmol/L sodium butyrate significantly increased p-ACC[(2.01±0.30)-fold,(1.66±0.18)-fold,(1.79±0.06)-fold vs.control group,respectively](P<0.01,P<0.05,P<0.01;F=4.807,7.507,7.028).Conclusion:Short chain fatty acids have the potential role of regulation glucose and lipid metabolism and blood glucose via Akt/GSK-3βand AMPK/ACC signal pathway.
作者
孙亚朝
邓邦利
牛文彦
SUN Ya-zhao;DENG Bang-li;NIU Wen-yan(Department of Immunology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China)
出处
《天津医科大学学报》
2023年第2期126-130,共5页
Journal of Tianjin Medical University
基金
国家自然科学基金面上项目(81670731,81870547)。
