Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders.
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.
Viollet
Benoit
B
Institut Cochin, INSERM U567, Department of Endocrinology, Metabolism and Cancer, 24 rue du Faubourg Saint Jacques, Paris 75014, France. viollet@cochin.inserm.fr
Foretz
Marc
M
Guigas
Bruno
B
Horman
Sandrine
S
Dentin
Renaud
R
Bertrand
Luc
L
Hue
Louis
L
Andreelli
Fabrizio
F
D055372:AMP-Activated Protein Kinases; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008107:Liver Diseases / Q000188:drug therapy / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*
D009097:Multienzyme Complexes; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose