AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives
Article first published online: 19 FEB 2009
© 2009 The Authors. Journal compilation © 2009 Scandinavian Physiological Society
Special Issue: THE 5TH INTERNATIONAL SYMPOSIUM ON AMPK 'AMPK IN SICKNESS AND HEALTH - FROM MOLECULE TO MAN'
Volume 196, Issue 1, pages 81–98, May 2009
How to Cite
Viollet, B., Guigas, B., Leclerc, J., Hébrard, S., Lantier, L., Mounier, R., Andreelli, F. and Foretz, M. (2009), AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiologica, 196: 81–98. doi: 10.1111/j.1748-1716.2009.01970.x
- Issue published online: 1 APR 2009
- Article first published online: 19 FEB 2009
- Received 20 September 2008, accepted 24 November 2008
- AMP-activated protein kinase;
- energy metabolism;
- fatty liver;
- hepatic glucose production;
- type 2 diabetes
As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome.