Document Detail


Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle.
MedLine Citation:
PMID:  23968980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Fatty acids (FAs) are the major substrate for energy production in the heart. Here, we hypothesize that capillary endothelial fatty acid binding protein 4 (FABP4) and FABP5 play an important role in providing sufficient FAs to the myocardium.
APPROACH AND RESULTS: Both FABP4/5 were abundantly expressed in capillary endothelium in the heart and skeletal muscle. The uptake of a FA analogue, 125I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid, was significantly reduced in these tissues in double-knockout (DKO) mice for FABP4/5 compared with wild-type mice. In contrast, the uptake of a glucose analogue, 18F-fluorodeoxyglucose, was remarkably increased in DKO mice. The expression of transcripts for the oxidative catabolism of FAs was reduced during fasting, whereas transcripts for the glycolytic pathway were not altered in DKO hearts. Notably, metabolome analysis revealed that phosphocreatine and ADP levels were significantly lower in DKO hearts, whereas ATP content was kept at a normal level. The protein expression levels of the glucose transporter Glut4 and the phosphorylated form of phosphofructokinase-2 were increased in DKO hearts, whereas the phosphorylation of insulin receptor-β and Akt was comparable between wild-type and DKO hearts during fasting, suggesting that a dramatic increase in glucose usage during fasting is insulin independent and is at least partly attributed to the post-transcriptional and allosteric regulation of key proteins that regulate glucose uptake and glycolysis.
CONCLUSIONS: Capillary endothelial FABP4/5 are required for FA transport into FA-consuming tissues that include the heart. These findings identify FABP4/5 as promising targets for controlling the metabolism of energy substrates in FA-consuming organs that have muscle-type continuous capillary.
Authors:
Tatsuya Iso; Kazuhisa Maeda; Hirofumi Hanaoka; Toshihiro Suga; Kosaku Goto; Mas Rizky A A Syamsunarno; Takako Hishiki; Yoshiko Nagahata; Hiroki Matsui; Masashi Arai; Aiko Yamaguchi; Nada A Abumrad; Motoaki Sano; Makoto Suematsu; Keigo Endo; Gökhan S Hotamisligil; Masahiko Kurabayashi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-08-22
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  33     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-10-17     Completed Date:  2013-12-13     Revised Date:  2014-04-09    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2549-57     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Animals
Endothelium, Vascular / metabolism
Energy Metabolism / physiology*
Fatty Acid-Binding Proteins / genetics,  metabolism*
Fatty Acids / diagnostic use,  metabolism*,  pharmacokinetics
Fluorodeoxyglucose F18 / diagnostic use,  pharmacokinetics
Iodobenzenes / diagnostic use,  pharmacokinetics
Mice
Mice, Knockout
Muscle, Skeletal / metabolism*
Myocardium / metabolism*
Neoplasm Proteins / genetics,  metabolism*
Phosphocreatine / metabolism
Phosphofructokinase-2 / metabolism
Grant Support
ID/Acronym/Agency:
DK033301/DK/NIDDK NIH HHS; DK064360/DK/NIDDK NIH HHS; R01 DK033301/DK/NIDDK NIH HHS; R01 DK060022/DK/NIDDK NIH HHS; R01 DK064360/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fabp4 protein, mouse; 0/Fabp5 protein, mouse; 0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/Iodobenzenes; 0/Neoplasm Proteins; 020IUV4N33/Phosphocreatine; 0Z5B2CJX4D/Fluorodeoxyglucose F18; 116754-87-1/iodofiltic acid; 61D2G4IYVH/Adenosine Diphosphate; EC 2.7.1.105/Phosphofructokinase-2
Comments/Corrections

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