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Deletion of Hepatic AMPK Leads to Metabolic Inflexibility in Low‐ and High‐Protein Diets but Not in Normo‐Protein Diet
Author(s) -
ChalvonDemersay Tristan,
Even Patrick Christian,
Chaumontet Catherine,
Piedcoq Julien,
Viollet Benoit,
Gaudichon Claire,
Tomé Daniel,
Foretz Marc,
AzzoutMarniche Dalila
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.969.21
Subject(s) - ampk , medicine , endocrinology , ingestion , triglyceride , protein kinase a , chemistry , beta oxidation , meal , fgf21 , fatty acid , metabolism , amp activated protein kinase , biology , biochemistry , kinase , cholesterol , fibroblast growth factor , receptor
The AMP‐activated protein kinase (AMPK) is involved in energy signalling and in the control of the protein synthesis in the liver. The present study attempted to define the role of this ubiquitous kinase in the adaptation of energy metabolism in response to changes in the protein content of the diet. 52 wild‐type mice (WT) and 46 KO‐AMPK liver specific male mice (KO LS ) were separated in 3 groups fed during 3 weeks with a low (LP‐5%), normal (NP‐14%) or high (HP‐55%) protein diet. Food intake and changes in body composition were measured throughout the experiment. At the end of the first week, changes in the rates of glucose and fatty acid oxidations (indirect calorimetry) were followed during 6 hours after ingestion of a 1g‐calibrated meal of their test‐diets given after an overnight fast. At the end of the experiment, the same test‐meal procedure was repeated and mice were killed either two or four hours after meal onset for measurements of hepatic gene expression and triglyceride content. Two hours after ingestion of the LP or HP test‐meals, KO LS mice showed smaller increase in glucose oxidation and decrease in fatty acid oxidation than WT mice. Food intake, plasmatic concentration of FGF21 (Fibroblast growth factor‐21), hepatic triglyceride content and expression of genes involved in fatty acid oxidation were not altered. In contrast, in NP‐fed mice, glucose and fatty acid oxidation profiles did not differ between the WT and KO LS mice. Intriguingly, the results showed an increase in cumulative food intake and plasma FGF21 levels in NP‐fed KO LS mice, these mice also displayed an increase in hepatic triglyceride content associated with higher expressions of genes involved in liver fatty acid oxidation and ketogenesis. Taken together, these results show that the consequences of AMPK deletion on energy metabolism depend on the protein content of the diet. In NP‐fed mice, deletion of AMPK in the liver led to an adaptation of liver metabolism resulting in an increased secretion of FGF21 and changes in gene expression encoding proteins involved in liver fatty acid oxidation and ketogenesis. These changes possibly compensated for the absence of hepatic AMPK as these mice exhibited normal post‐prandial changes in glucose and lipid oxidation. In contrast, in LP‐and HP‐fed mice, the lack of adjustment in liver metabolism in KO LS mice resulted in a metabolic inflexibility leading to reduced amplitude of meal‐induced changes in glucose and fatty acid oxidation.