부산대학교 도서관

Objective 5’AMP-Activated Protein Kinase (AMPK) is a metabolic regulator which increases catabolic processes and decreases anabolic ones. Recently we reported that AMPK activity and its downstream signals are impaired in the fatty liver from a generalized lipodystrophic mice and that leptin activates hepatic AMPK with improvement of fatty liver via α1-receptors in vivo. We here further investigated to elucidate significance of hepatic AMPK in the sympathetic metabolic action. Methods The effects of an α1-agonist, phenylephrine were studied in isolated primary hepatocytes, normal and high fat diet (HFD)-fed C57BL/6J mice. Results Phenylephrine activated AMPK in isolated primary hepatocytes and liver from normal mice in vivo. AICAR, phenylephrine or a β-agonist, isoproterenol diminished TG content in the hepatocytes. The AICAR and phenylephrine-induced TG reduction were completely inhibited by BML-275, an AMPK inhibitor, while the effect of isoproterenol was not affected. AMPK inhibition increased glucose production under the phenylephrine stimulation. Phenylephrine also activated hepatic AMPK even in HFD-fed mice. Continuous administration of phenylephrine ameliorated glucose tolerance, insulin resistance and fatty liver in HFD-fed mice with activating hepatic AMPK. Conclusion We found that the α1-adrenoreceptor stimulation causes AMPK activation in hepatocytes. The hepatic AMPK activation mediates reduction of TG content by α-adrenergic stimulation while it counteracts the hepatic glucose production. In addition, α-adrenergic stimulation improved fatty liver, insulin resistance and hyperglycemia in insulin resistant mice, which is supposed to be mediated by hepatic AMPK activation at least partly. In conclusion, hepatic AMPK should play significant roles in the metabolic regulation by sympathetic nervous system.