Constitutive AMPK activation prevents HCC through inhibition of HNF4a

The AMP-activated protein kinase (AMPK) is a master regulator of metabolism, and its activation has been proposed as a therapeutic strategy for treating metabolic disorders. However, while AMPK activity is downregulated in HCC, the precise role of AMPK in HCC development has not been clearly delineated.

Here, we investigated the ability of constitutive AMPK activation to prevent HCC development using a constitutively active AMPK transgenic mouse model and a pharmacological AMPK activator. We observed that AMPK activation significantly reduced tumor formation in both diethylnitrosamine (DEN)-induced and streptozocin-induced (STAM) models of HCC via altered bile acid metabolism and inhibition of hepatic nuclear factor alpha (HNF4) signaling.