AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice.

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State: Public
Version: Final published version
Serval ID
serval:BIB_1E26E53BF1FE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice.
Journal
Molecular metabolism
Author(s)
Carneiro L., Asrih M., Repond C., Sempoux C., Stehle J.C., Leloup C., Jornayvaz F.R., Pellerin L.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Publication state
Published
Issued date
12/2017
Peer-reviewed
Oui
Volume
6
Number
12
Pages
1625-1633
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Hepatic steatosis is the first step leading to non-alcoholic fatty liver disease, which represents a major complication of obesity. Here, we show that MCT1 haploinsufficient mice resist to hepatic steatosis development when fed a high fat diet. They exhibit a reduced hepatic capacity to metabolize monocarboxylates such as lactate compared to wildtype mice.
To understand how this resistance to steatosis develops, we used HFD fed wildtype mice with hepatic steatosis and MCT1 haploinsufficient mice to study hepatic metabolism.
AMPK is constitutively activated in the liver of MCT1 haploinsufficient mice, leading to an inactivation of SREBP1. Therefore, expression of key transcription factors for lipid metabolism, such as PPARα and γ, CHREB, or SREBP1 itself, as well as several enzymes including FAS and CPT1, was not upregulated in these mice when fed a high fat diet. It is proposed that reduced hepatic lactate metabolism is responsible for the protection against hepatic steatosis in MCT1 haploinsufficient mice via a constitutive activation of AMPK and repression of several major elements involved in hepatic lipid metabolism.
Our results support a role of increased lactate uptake in hepatocytes during HFD that, in turn, induce a metabolic shift stimulating SREBP1 activity and lipid accumulation.
Keywords
Animals, Fatty Liver/genetics, Fatty Liver/metabolism, Haploinsufficiency, Lactic Acid/metabolism, Lipid Metabolism, Liver/metabolism, Male, Mice, Monocarboxylic Acid Transporters/genetics, Monocarboxylic Acid Transporters/metabolism, Protein Kinases/metabolism, Sterol Regulatory Element Binding Protein 1/metabolism, Symporters/genetics, Symporters/metabolism, Diabetes, Lactate, Liver, NAFLD, Obesity
Pubmed
Web of science
Open Access
Yes
Create date
03/11/2017 13:26
Last modification date
20/08/2019 13:54
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