AMPK: Lessons from transgenic and knockout animals.
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.
Viollet
Benoit
B
Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Department Endocrinology, Metabolism and Cancer, Paris, France. viollet@cochin.inserm.fr
Athea
Yoni
Y
Mounier
Remi
R
Guigas
Bruno
B
Zarrinpashneh
Elham
E
Horman
Sandrine
S
Lantier
Louise
L
Hebrard
Sophie
S
Devin-Leclerc
Jocelyne
J
Beauloye
Christophe
C
Foretz
Marc
M
Andreelli
Fabrizio
F
Ventura-Clapier
Renee
R
Bertrand
Luc
L
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000201:enzymology / Q000502:physiology; D004734:Energy Metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000201:enzymology; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011487:Protein Conformation
D007004:Hypoglycemic Agents; D055372:AMP-Activated Protein Kinases