AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats
AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats
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DOI：
10.1152/ajpendo.00144.2005
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发表时间：
2005-11-01
影响因子：
5.1
通讯作者：
Ruderman, NB
中科院分区：
文献类型：
--
作者：
Assifi, MM;Suchankova, G;Ruderman, NB
丙二酰辅酶A浓度的急性增加在介导禁食后再进食期间许多组织中发生的脂肪酸氧化减少中起关键作用。在这项研究中，我们评估是否可以通过丙二酰辅酶A脱羧酶（MCD），以及乙酰辅酶A羧化酶（ACC）介导的肝丙二酰辅酶A的这种增加。此外，我们还研究了ACC，MCD和其他酶的活性变化，这些酶支配脂肪酸和甘油酯的合成，与燃料传感酶AMP活化蛋白激酶（AMPK）的活性变化在时间上有关。大鼠饥饿48小时，再喂碳水化合物饲料的饮食1，3，12，和24小时进行了研究。再喂食导致AMPK α 1亚型活性在1小时内降低40%，AMPK α 1活性进一步降低，AMPK α 2活性在1至24小时之间降低。在1小时，AMPK活性的降低与ACC α 1亚型活性的8倍增加和MCD活性的30%降低相关，这两种酶被认为是由AMPK调节的。此外，丙二酰辅酶A的浓度增加了50%。在1和3小时之间的再喂养，额外的增加，ACC的活性和减少MCD观察到的，是一个进一步的两倍增加丙二酰辅酶A。脂肪酸合成酶的活性（60%）和丰度（12倍）的增加主要发生在3和24 h之间，线粒体sn-甘油-3-磷酸酰基转移酶（GPAT）和酰基辅酶A：二酰基甘油酰基转移酶（DGAT）的活性在12和24 h增加。结果强烈表明，MCD的活性的早期变化，以及ACC，有助于增加肝丙二酰辅酶A在饥饿refed大鼠。他们还表明，这些酶的变化，以及后来调节脂肪酸和甘油酯合成的酶的增加，可以通过AMPK来协调。
Acute increases in the concentration of malonyl-CoA play a pivotal role in mediating the decrease in fatty acid oxidation that occurs in many tissues during refeeding after a fast. In this study, we assess whether such increases in malonyl-CoA in liver could be mediated by malonyl-CoA decarboxylase (MCD), as well as acetyl-CoA carboxylase (ACC). In addition, we examine how changes in the activity of ACC, MCD, and other enzymes that govern fatty acid and glycerolipid synthesis relate temporally to alterations in the activities of the fuel-sensing enzyme AMP-activated protein kinase ( AMPK). Rats starved for 48 h and refed a carbohydrate chow diet for 1, 3, 12, and 24 h were studied. Refeeding caused a 40% decrease in the activity of the alpha 1-isoform of AMPK within 1 h, with additional decreases in AMPK alpha 1 activity and a decrease in AMPK alpha 2 occurring between 1 and 24 h. At 1 h, the decrease in AMPK activity was associated with an eightfold increase in the activity of the alpha 1-isoform of ACC and a 30% decrease in the activity of MCD, two enzymes thought to be regulated by AMPK. Also, the concentration of malonyl-CoA was increased by 50%. Between 1 and 3 h of refeeding, additional increases in the activity of ACC and decreases in MCD were observed, as was a further twofold increase in malonyl-CoA. Increases in the activity (60%) and abundance (12-fold) of fatty acid synthase occurred predominantly between 3 and 24 h and increases in the activity of mitochondrial sn-glycerol-3-phosphate acyltransferase (GPAT) and acyl-CoA: diaclyglycerol acyltransferase (DGAT) at 12 and 24 h. The results strongly suggest that early changes in the activity of MCD, as well as ACC, contribute to the increase in hepatic malonyl-CoA in the starved-refed rat. They also suggest that the changes in these enzymes, and later occurring increases in enzymes regulating fatty acid and glycerolipid synthesis, could be coordinated by AMPK.