[Frontiers in Bioscience 14, 19-44, January 1, 2009]

AMPK: Lessons from transgenic and knockout animals

Benoit Viollet1,2, Yoni Athea3,4, Remi Mounier1,2, Bruno Guigas5,6, Elham Zarrinpashneh7, Sandrine Horman5, Louise Lantier1,2, Sophie Hebrard1,2, Jocelyne Devin-Leclerc1,2, Christophe Beauloye7, Marc Foretz1,2, Fabrizio Andreelli1,2,8, Renée Ventura-Clapier3,4, Luc Bertrand7

1Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Department Endocrinology, Metabolism and Cancer, Paris, France, 2Inserm, U567, Paris, France, 3Inserm, U769, Chatenay-Malabry, France, 4Universite Paris-Sud, Chatenay-Malabry, France, 5Universite catholique de Louvain and Institute of Cellular Pathology, Hormone and Metabolic Research Unit, Brussels, Belgium, 6Leiden University Medical Center, Department of Mol Cell Biology, Leiden, Netherlands, 7Universite catholique de Louvain, Division of cardiology, Brussels, Belgium, 8Inserm U695, IFR Xavier Bichat, Paris, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Structure and function of AMPK complexes
4. Development of animal models for the study of AMPK functions
5. Distinct physiological roles for AMPK subunits in the control of energy metabolism and insulin sensitivity
6. Role of AMPK in the control of hepatic metabolism
7. Role of AMPK in adipose tissue
8. Role of AMPK in skeletal muscle physiology
9. Role of AMPK in the heart
10. Role of AMPK in vascular reactivity
11. Role of AMPK in the hypothalamus
12. New insights in AMPK functions from non-mammalian animal model systems
12.1. Drosophila melanogaster
12.2. Caenorhabditis elegans 
13. Action of anti-diabetic drugs on the AMPK pathway
14. Relationship between adiponectin and AMPK pathways: insights from KO models
15. Perspectives
16. Acknowledegments
17. References

1. ABSTRACT

AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, has been proposed to function as a 'fuel gauge' to monitor cellular energy status in response to nutritional environmental variations. AMPK system is a regulator of energy balance that, once activated by low energy status, switches on ATP-producing catabolic pathways (such as fatty acid oxidation and glycolysis), and switches off ATP-consuming anabolic pathways (such as lipogenesis), both by short-term effect on phosphorylation of regulatory proteins and by long-term effect on gene expression. Numerous observations obtained with pharmacological activators and agents that deplete intracellular ATP have been supportive of AMPK playing a role in the control of energy metabolism but none of these studies have provided conclusive evidence. Relatively recent developments in our understanding of precisely how AMPK complexes might operate to control energy metabolism is due in part to the development of transgenic and knockout mouse models. Although there are inevitable caveats with genetic models, some important findings have emerged. In the present review, we discuss recent findings obtained from animal models with inhibition or activation of AMPK signaling pathway.