AMPK inhibition in health and disease.

Benoit Viollet (1) , Sandrine Horman (2) , Jocelyne Leclerc (1) , Louise Lantier (1) , Marc Foretz (1) , Marc Billaud (3) , Shailendra Giri (4) , Fabrizio Andreelli (1)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 Division of cardiology
3 GMSC - Génétique moléculaire, signalisation et cancer
4 Department of Experimental Pathology

All living organisms depend on dynamic mechanisms that repeatedly reassess the status of amassed energy, in order to adapt energy supply to demand. The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer has emerged as an important integrator of signals managing energy balance. Control of AMPK activity involves allosteric AMP and ATP regulation, auto-inhibitory features and phosphorylation of its catalytic (alpha) and regulatory (beta and gamma) subunits. AMPK has a prominent role not only as a peripheral sensor but also in the central nervous system as a multifunctional metabolic regulator. AMPK represents an ideal second messenger for reporting cellular energy state. For this reason, activated AMPK acts as a protective response to energy stress in numerous systems. However, AMPK inhibition also actively participates in the control of whole body energy homeostasis. In this review, we discuss recent findings that support the role and function of AMPK inhibition under physiological and pathological states.

Mots clés: Energy balance; metabolism; inhibition; AMPK; metabolic diseases

Domaines: Endocrinologie et métabolisme

Benoit Viollet, Sandrine Horman, Jocelyne Leclerc, Louise Lantier, Marc Foretz, et al.. AMPK inhibition in health and disease.. Critical Reviews in Biochemistry and Molecular Biology, 2010, 45 (4), pp.276-95. ⟨10.3109/10409238.2010.488215⟩. ⟨inserm-00489848⟩