AMP-activated protein kinase and its multifaceted regulation of hepatic metabolism

The current review summarizes recent advancements in our mechanistic and physiological understanding of the energy sensing AMP-activated protein kinase (AMPK) and its regulation of select aspects of hepatic metabolism.

A highly conserved serine/threonine kinase, AMPK governs a multitude of cellular process to activate catabolic and inhibit anabolic pathways. Recent work has provided clarity as to the importance and contribution of the AMPK signaling cascade to various aspects of cellular metabolism, including lipid homeostasis, hepatic glucose production, mitochondrial metabolism, and autophagy.

With more than 60 confirmed substrates, the physiological significance of AMPK signaling has been difficult to ascertain. The generation of targeted knock-in mutations on key AMPK substrates has begun to shed light on this complex system. Future studies are needed to further decipher the complexity, significance, and potential therapeutic targeting of hepatic AMPK signaling.