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Open AccessArticle

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

by 1,2,3,*, 4 and 1,2,3,*
INSERM, U1016, Institut Cochin, Département d’Endocrinologie Métabolisme et Diabète, 24, rue du Faubourg Saint Jacques, 75014 Paris, France
CNRS, UMR8104, 75014 Paris, France
Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
UMR PNCA, AgroParisTech, INRA, Université Paris-Saclay, 75005 Paris, France
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(9), 2826;
Received: 1 August 2018 / Revised: 13 September 2018 / Accepted: 15 September 2018 / Published: 19 September 2018
(This article belongs to the Special Issue AMP-Activated Protein Kinase Signalling)
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 [C14]-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. View Full-Text
Keywords: AMPK; liver; lipid metabolism; fatty acid oxidation; indirect calorimetry AMPK; liver; lipid metabolism; fatty acid oxidation; indirect calorimetry
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MDPI and ACS Style

Foretz, M.; Even, P.C.; Viollet, B. AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo. Int. J. Mol. Sci. 2018, 19, 2826.

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