Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes
Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes
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DOI：
10.1042/bj20061479
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发表时间：
2007-05-01
影响因子：
4.1
通讯作者：
Goodyear, Laurie J.
中科院分区：
文献类型：
--
作者：
Koh, Ho-Jin;Hirshman, Michael F.;Goodyear, Laurie J.
运动增加人类和大鼠脂肪细胞中AMPK（AMP活化蛋白激酶）的活性，但这种活化的潜在分子机制和功能后果尚不清楚。由于肾上腺素（epinephrine）浓度随运动而增加，在本研究中，我们假设肾上腺素激活脂肪细胞中的AMPK。我们表明，单次运动会增加大鼠脂肪细胞中AMPK α 1和α 2的活性以及ACC（乙酰辅酶A羧化酶）Ser（79）磷酸化。类似于运动，肾上腺素治疗在体内增加AMPK活性和ACC磷酸化。用β受体阻滞剂普萘洛尔预处理大鼠完全阻断了运动诱导的AMPK激活。AMPK活性的增加与运动和肾上腺素治疗在体内伴随着AMP/ATP比值的增加。肾上腺素孵育分离的脂肪细胞也增加了AMP/ATP比和AMPK活性，普萘洛尔阻断了这种作用。肾上腺素孵育增加了分离的脂肪细胞中的脂解，而AMPK抑制剂化合物C减弱了这种作用。最后，AMPK α 1和α 2活性在训练6周的大鼠脂肪细胞中显著增加，表明AMPK在与慢性运动相关的肥胖减少中的潜在作用。总之，急性和慢性运动是大鼠脂肪细胞AMPK活性的重要调节剂。我们的研究结果表明，肾上腺素在运动刺激的脂肪细胞AMPK α 1和α 2活性中起着关键作用，AMPK可以在脂解的调节中发挥作用。
Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPK alpha 1 and alpha 2 activities and ACC (acetyl-CoA carboxylase) Ser(79) phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the beta-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPK alpha 1 and alpha 2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPK alpha 1 and alpha 2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis.