【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。更多还原

【Abstract】 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-3β and AMPK/ACC signal pathway.更多还原