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Topical Review |
1 Institut Cochin, INSERM U567, CNRS UMR 8104, Université Paris 5, Department of Endocrinology, Metabolism and Cancer, Paris, France
2 Hormone and Metabolic Research Unit, Institute of Cellular Pathology, Université catholique de Louvain, Brussels, Belgium
3 Division of Cardiology, School of Medicine, Université catholique de Louvain, Brussels, Belgium
It is now becoming evident that the liver has an important role in the control of whole body metabolism of energy nutrients. In this review, we focus on recent findings showing that AMP-activated protein kinase (AMPK) plays a major role in the control of hepatic metabolism. AMPK integrates nutritional and hormonal signals to promote energy balance by switching on catabolic pathways and switching off ATP-consuming pathways, both by short-term effects on phosphorylation of regulatory proteins and by long-term effects on gene expression. Activation of AMPK in the liver leads to the stimulation of fatty acid oxidation and inhibition of lipogenesis, glucose production and protein synthesis. Medical interest in the AMPK system has recently increased with the demonstration that AMPK could mediate some of the effects of the fat cell-derived adiponectin and the antidiabetic drugs metformin and thiazolidinediones. These findings reinforce the idea that pharmacological activation of AMPK may provide, through signalling and metabolic and gene expression effects, a new strategy for the management of metabolic hepatic disorders linked to type 2 diabetes and obesity.
(Received 27 February 2006;
accepted after revision 26 April 2006;
first published online 27 April 2006)
Corresponding author B. Viollet: Institut Cochin, INSERM U567, Department of Endocrinology, Metabolism and Cancer, 24 rue du Faubourg Saint Jacques, Paris 75014, France. Email: viollet{at}cochin.inserm.fr
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