Merrill G F, Kurth E J, Hardie D G, Winder W W
Department of Biological Sciences, Rutgers University, New Brunswick, New Jersey 98903, USA.
Am J Physiol. 1997 Dec;273(6):E1107-12. doi: 10.1152/ajpendo.1997.273.6.E1107.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 microU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.
5-氨基咪唑-4-甲酰胺核苷（AICAR）此前已有报道称其可被细胞摄取并磷酸化形成ZMP，一种5'-AMP的类似物。本研究旨在确定AICAR是否能激活骨骼肌中的AMP激活蛋白激酶（AMPK），进而使乙酰辅酶A羧化酶（ACC）磷酸化，降低丙二酰辅酶A水平，并增加脂肪酸氧化。用含有4%牛血清白蛋白、洗涤过的牛红细胞、200微单位/毫升胰岛素和10毫摩尔葡萄糖的Krebs-Henseleit碳酸氢盐溶液灌注大鼠后肢，灌注液中添加或不添加AICAR（0.5 - 2.0毫摩尔）。结果发现，用含有AICAR的培养基灌注可激活骨骼肌中的AMPK，使ACC失活，并降低丙二酰辅酶A水平。用2毫摩尔AICAR灌注后肢45分钟，脂肪酸氧化增加了2.8倍，葡萄糖摄取显著增加。AICAR灌注组与对照组后肢的氧摄取量未观察到差异。这些结果证明，肌肉中丙二酰辅酶A含量的降低可提高脂肪酸氧化速率。
