AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo

Marc Foretz (1) , Patrick P. Even (2) , Benoit Viollet (1)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 PNCA - Physiologie de la Nutrition et du Comportement Alimentaire

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver, achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C-14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

Mots clés: ampk; liver; lipid metabolism; fatty acid oxidation; indirect calorimetry; protein-kinase; liver-disease; homeostasis; steatosis; aicar

Mots clés: mitochondrial

Domaines: Biologie moléculaire; Organisation et fonctions cellulaires [q-bio.SC]; Endocrinologie et métabolisme

Marc Foretz, Patrick P. Even, Benoit Viollet. AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo. International Journal of Molecular Sciences, 2018, 19 (9), pp.2826. ⟨10.3390/ijms19092826⟩. ⟨hal-02346754⟩