In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside （AICAR） on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver （a low ketogenic and lipogenic ti...In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside （AICAR） on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver （a low ketogenic and lipogenic tissue） was tested Incubation of hepatocytes with AICAR （0.5 raM） in the presence of ] mM of carnitine and 10 mM of glucose for 1 hour at 37℃ had no significant effect on total [1-14C]-palrnitate （0.5 mM） oxidation （14CO2 and 14C-Acid soluble products （ASP））. Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyI-CoA （10 MM） assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased 14CO2 production by 18% compared to control （p 〈 0.06）. The reduction of labeled carboxylic carbon accumulated in C02 caused a significant difference in distribution of oxidative products between 14C02 and 14C-ASP （p 〈 0.03） compared with the control. It was also noticed that acetyI-CoA carboxylase （ACC） was increased by AICAR （p 〈 0.03）, indicating that ACC might drive acetyI-CoA toward fatty acid synthesis pathway and induce an increase in distribution of fatty acid carbon to 14C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO2 and ASP, but further promoted ACC activity. The increased ACC activity was 70% higher than in the control group when citrate was absent in the reaction medium and was 30% higher when citrate was present in the medium. Our results suggest that AICAR may affect the distribution of metabolic products from fatty acid oxidation by changing ACC activity in hepatocyte isolated from suckled neonatal piglets; however, the basis for the increase in ACC activity elicited by AICAR is not apparent.展开更多
腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)是细胞能量调节的关键激酶,近期研究表明AMPK也在炎症这一高耗能分子反应中发挥重要调控作用。目前常用的AMPK激活剂有5-氨基咪唑-4-甲酰胺核苷酸(5-aminoimidazole-4-carboxami...腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)是细胞能量调节的关键激酶,近期研究表明AMPK也在炎症这一高耗能分子反应中发挥重要调控作用。目前常用的AMPK激活剂有5-氨基咪唑-4-甲酰胺核苷酸(5-aminoimidazole-4-carboxamide ribonucleotide, AICAR)和A-769662,此外二甲双胍及脂联素发挥生物活性也与激活AMPK密切相关。大量研究表明,这些激活剂可在急性肺损伤、哮喘、结肠s炎、肝炎、动脉粥样硬化等多种炎症相关性疾病动物模型中发挥有效的保护作用。因而,AMPK激活剂在炎症相关性疾病的防治中具有广阔的研发和应用前景。展开更多
基金supported by National Research Initiative Competitive Grant no. 2007-35206-17897 from the USDA National Institute of Food and Agriculture
文摘In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside （AICAR） on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver （a low ketogenic and lipogenic tissue） was tested Incubation of hepatocytes with AICAR （0.5 raM） in the presence of ] mM of carnitine and 10 mM of glucose for 1 hour at 37℃ had no significant effect on total [1-14C]-palrnitate （0.5 mM） oxidation （14CO2 and 14C-Acid soluble products （ASP））. Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyI-CoA （10 MM） assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased 14CO2 production by 18% compared to control （p 〈 0.06）. The reduction of labeled carboxylic carbon accumulated in C02 caused a significant difference in distribution of oxidative products between 14C02 and 14C-ASP （p 〈 0.03） compared with the control. It was also noticed that acetyI-CoA carboxylase （ACC） was increased by AICAR （p 〈 0.03）, indicating that ACC might drive acetyI-CoA toward fatty acid synthesis pathway and induce an increase in distribution of fatty acid carbon to 14C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO2 and ASP, but further promoted ACC activity. The increased ACC activity was 70% higher than in the control group when citrate was absent in the reaction medium and was 30% higher when citrate was present in the medium. Our results suggest that AICAR may affect the distribution of metabolic products from fatty acid oxidation by changing ACC activity in hepatocyte isolated from suckled neonatal piglets; however, the basis for the increase in ACC activity elicited by AICAR is not apparent.
基金supported by grants from the National Natural Science Foundation of China (No. 81671953 81370179)+1 种基金the Chongqing Research Program of Basic Research and Frontier Technology China (No. cstc-2017jcyjAX0098)
文摘腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)是细胞能量调节的关键激酶,近期研究表明AMPK也在炎症这一高耗能分子反应中发挥重要调控作用。目前常用的AMPK激活剂有5-氨基咪唑-4-甲酰胺核苷酸(5-aminoimidazole-4-carboxamide ribonucleotide, AICAR)和A-769662,此外二甲双胍及脂联素发挥生物活性也与激活AMPK密切相关。大量研究表明,这些激活剂可在急性肺损伤、哮喘、结肠s炎、肝炎、动脉粥样硬化等多种炎症相关性疾病动物模型中发挥有效的保护作用。因而,AMPK激活剂在炎症相关性疾病的防治中具有广阔的研发和应用前景。
