Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle

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

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2549-2557
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number11
DOIs
Publication statusPublished - 2013 Nov 1

Keywords

  • capillaries
  • endothelial cells
  • fatty acid binding proteins
  • fatty acids
  • glucose
  • metabolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle'. Together they form a unique fingerprint.

  • Cite this

    Iso, T., Maeda, K., Hanaoka, H., Suga, T., Goto, K., Syamsunarno, M. R. A. A., Hishiki, T., Nagahata, Y., Matsui, H., Arai, M., Yamaguchi, A., Abumrad, N. A., Sano, M., Suematsu, M., Endo, K., Hotamisligil, G. S., & Kurabayashi, M. (2013). Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(11), 2549-2557. https://doi.org/10.1161/ATVBAHA.113.301588