Metabolic adaptations to fasting and chronic caloric restriction in heart, muscle, and liver do not include changes in AMPK activity
Metabolic adaptations to fasting and chronic caloric restriction in heart, muscle, and liver do not include changes in AMPK activity
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DOI：
10.1152/ajpendo.00172.2004
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发表时间：
2004-11-01
影响因子：
5.1
通讯作者：
Saupe, KW
中科院分区：
文献类型：
--
作者：
Gonzalez, AA;Kumar, R;Saupe, KW
单磷酸腺苷激活蛋白激酶 (AMPK) 的激活在细胞适应体外营养缺乏方面发挥着核心作用。 AMPK 活性与营养状况之间的这种联系提出了 AMPK 在急性和慢性营养应激的代谢适应中发挥作用的可能性。然而，营养应激对体内 AMPK 活性的影响尚未得到系统评估。为了解决这个问题，我们测量了 24 小时禁食和 4 个月热量限制 (CR) 对小鼠心脏、骨骼肌和肝脏 AMPKα1 和 -α2 活性的影响。尽管禁食引起了体重、血浆瘦素和游离脂肪酸的预期变化，但它并没有增加心脏或骨骼肌中的 AMPK 活性，仅使肝脏 AMPK 活性增加了大约 20%（P = 0.10）。同样，CR 引起了体重、血浆瘦素和游离脂肪酸的预期变化，但没有改变这三种组织中任何一个的 AMPK 活性。尽管 CR 没有改变肝脏 AMPK 活性，但它显着降低了磷酸化乙酰辅酶 A 羧化酶的量，并且发现这是由于蛋白质表达减少所致。在任何组织中 AMPK 活性没有变化的情况下，四组小鼠的血浆瘦素（一种假定的 AMPK 激活剂）变化了八倍。我们的结论是，尽管对禁食和 CR 的代谢适应包括血浆瘦素浓度和磷酸化乙酰辅酶 A 羧化酶的变化，但这些影响的发生并不改变 AMPK 活性。
Activation of adenosine monophosphate-activated protein kinase ( AMPK) plays a central role in allowing cells to adapt to nutrient deprivation in vitro. This link between AMPK activity and nutritional status has raised the possibility that AMPK plays a role in the metabolic adaptation to acute and chronic nutritional stress. However, the effects of nutritional stress on AMPK activity in vivo have not been systematically evaluated. To address this, we measured the effects of 24 h of fasting and 4 mo of caloric restriction (CR) on AMPKalpha1 and -alpha2 activities in heart, skeletal muscle, and liver in mice. Although fasting caused the expected changes in body weight, plasma leptin, and free fatty acids, it did not increase AMPK activity in heart or skeletal muscle and only increased liver AMPK activity by similar to 20% ( P = 0.10). Likewise, CR caused the expected changes in body weight, plasma leptin, and free fatty acids but did not alter AMPK activity in any of the three tissues. Although CR did not alter liver AMPK activity, it dramatically decreased the amount of phosphorylated acetyl-CoA carboxylase, and this was found to be due to decreased protein expression. Plasma leptin, a putative activator of AMPK, varied eightfold across the four groups of mice in the absence of changes in AMPK activity in any tissue. We conclude that, although the metabolic adaptations to fasting and CR include changes in plasma leptin concentration and phosphorylated acetyl-CoA carboxylase, these effects occur without changes in AMPK activity.