Capillary Endothelial Fatty Acid Binding Proteins 4 and 5 Play a Critical Role in Fatty Acid Uptake in Heart and Skeletal Muscle

• DOI: 10.1161/atvbaha.113.301588
• Publication Date: 2013-08-23T04:37:07Z
• Authors: Tatsuya Iso; Kazuhisa Maeda; Hirofumi Hanaoka; Toshihiro Suga; Kosaku Goto; Mas Rizky A.A Sya...; Takako Hishiki; Yoshiko Nagahata; Hiroki Matsui; Masashi Arai; Aiko Yamaguchi; Nada A. Abumrad; Motoaki Sano; Makoto Suematsu; Keigo Endo; Gökhan S. Hotamis...; Masahiko Kurabayashi
• Keywords: Mice, Knockout; 0301 basic medicine; Phosphocreatine; Iodobenzenes; Phosphofructokinase-2; Myocardium; Fatty Acids; Fatty Acid-Binding Proteins; Neoplasm Proteins; Adenosine Diphosphate; Mice; 03 medical and health sciences; Fluorodeoxyglucose F18; Animals; Endothelium, Vascular; Energy Metabolism; Muscle, Skeletal

Objective— Fatty acids (FAs) are the major substrate for energy production in heart. Here, we hypothesize that capillary endothelial fatty acid binding protein 4 (FABP4) and FABP5 play an important role providing sufficient FAs to myocardium. Approach Results— Both FABP4/5 were abundantly expressed endothelium heart skeletal muscle. The uptake of a FA analogue, 125I-15-( p -iodophenyl)-3-(R,S)-methyl pentadecanoic acid, was significantly reduced these tissues double-knockout (DKO) mice compared with wild-type mice. In contrast, glucose 18F-fluorodeoxyglucose, remarkably increased DKO expression transcripts oxidative catabolism during fasting, whereas glycolytic pathway not altered hearts. Notably, metabolome analysis revealed phosphocreatine ADP levels lower hearts, ATP content kept at normal level. transporter Glut4 phosphorylated form phosphofructokinase-2 phosphorylation insulin receptor-β Akt comparable between hearts suggesting dramatic increase usage fasting is independent least partly attributed post-transcriptional allosteric regulation key proteins regulate glycolysis. Conclusions— Capillary required transport into FA-consuming include These findings identify as promising targets controlling metabolism substrates organs have muscle-type continuous capillary.