AMPK与代谢综合征

能量代谢失衡是肥胖和代谢综合征的主要原因。在调节细胞能量状态的蛋白激酶级联反应中,AMP激活的蛋白激酶(AMPK)是其中枢组成部分。AMPK的活性受AMP/ATP比值的调节。应激反应可通过ATP的产生减少或利用增加,使细胞内AMP/ATP的比值增加,从而激活AMPK。激活的AMPK可激发一系列的反应来恢复细胞内的能量平衡。AMPK可启动分解代谢途径,如脂肪酸氧化和糖酵解,从而增加ATP的产生,同时关闭合成代谢途径,如脂肪酸合成和蛋白合成,减少ATP的消耗。AMPK不仅可以在细胞水平作为能量的感受器,还可以通过激素和细胞因子,如瘦素、脂联素和ghrelin来参与调节机体的能量消耗和能量摄入。新近的研究发现二甲双胍类抗糖尿病药物可以激活AMPK,调节糖代谢,提示AMPK有可能在预防机体发生代谢性疾病,如代谢综合征、肥胖和2型糖尿病中起作用。因而,阐明AMPK在不同组织及整体水平上对能量贮存与消耗的调节是今后该领域的研究热点,并且AMPK的级联反应有可能成为治疗肥胖和代谢综合征的有效靶标。

AMPK and metabolic syndrome

Imbalance of energy metabolism is a major cause for metabolic syndrome. AMP-activated protein kinase AMPK is a central component of a protein kinase cascade that plays a pivotal role in the regulation of intracellular energy status.AMPK activity is a response to the ratio of AMP/ATP in the cell.When a stress causes an inhibition of ATP production or an increase of ATP consumption,cellular AMP/ATP ratio increases,AMPK is activated.Once activated,AMPK initiates a series of responses to restore the energy balance within the cell.AMPK switches on catabolic pathways,such as fatty acid oxidation and glycolysis,to generate ATP,and switches off anabolic pathways,such as fatty acid synthesis and protein synthesis,to reduce ATP-consumption.Therefore,AMPK functions in an ideal position not only as an energy sensor at cellular level,but also as a pivotal player in the regulating pathways that control both energy expenditure and energy intake,in particular by mediating the effects of hormones and cytokines such as leptin,adiponectin and ghrelin.The recent finding that anti-diabetic drug metformin and TZD regulates glucose metabolism through the activation of AMPK suggested a possible role of AMPK in protecting the body from metabolic diseases such as metabolic syndrome,obesity and type 2 diabetes.Thus,further work in this field in the next several years will be necessary in order to fullyunderstand the role of AMPK in regulating the balance of energy storage and expenditure in different tissues and at the whole body level.Targeting to AMPK cascade would also have potentially pharmaceutical application for obesity and metabolic syndrome.