Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice
| Autor: | Hiroshi Akazawa, Kazuhiro Nakatani, Shizuya Yamashita, Eku Shimosegawa, Yasushi Sakata, Ryota Kawase, Tohru Ohama, Masao Imaizumi, Atsuhiko T. Naito, Toru Oka, Jun Hatazawa, Takuya Kobayashi, Hajime Nakaoka, Takeshi Okada, Daisaku Masuda, Tadashi Watabe, Masahiro Koseki, Makoto Nishida, Yinghong Zhu, Issei Komuro, Masami Sairyo |
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| Rok vydání: | 2015 |
| Předmět: |
CD36 Antigens
medicine.medical_specialty Phosphocreatine Endocrinology Diabetes and Metabolism Glucose uptake PDK4 Citrate (si)-Synthase Ketone Bodies Biology Mice chemistry.chemical_compound Adenosine Triphosphate Endocrinology Internal medicine medicine Animals Mice Knockout Glucose Transporter Type 1 Glucose Transporter Type 4 3-Hydroxybutyric Acid Fatty acid metabolism Myocardium Glucose transporter Mice Inbred C57BL Glucose chemistry Heart-type fatty acid binding protein Ketone bodies biology.protein GLUT1 Energy Metabolism GLUT4 |
| Zdroj: | Metabolism. 64:1165-1174 |
| ISSN: | 0026-0495 |
| Popis: | Aims CD36 is an important transporter of long-chain fatty acids (LCFAs) in the myocardium. As we have reported previously, CD36-deficient patients demonstrate a marked reduction in myocardial uptake of 123I-15-(p-iodophenyl)-(R, S)-methyl pentadecanoic acid (BMIPP), which is an analog of LCFAs, while myocardial 18 F-fluorodeoxy-glucose (FDG) uptake is increased. However, it has not been clarified whether energy provision is preserved in patients with CD36 deficiency. The aims of the current study were to investigate the myocardial uptake of glucose and alterations in myocardial metabolites in wild-type (WT) and CD36 knockout (KO) mice. Methods and results High-resolution positron emission tomography (PET) demonstrated markedly enhanced glucose uptake in KO mouse hearts compared with those of WT mice in real-time. The myocardial protein expression of glucose transporter protein 1 (GLUT1) was significantly enhanced in KO mice compared to WT mice, whereas that of GLUT4 was not altered. While the myocardial expression of genes involved in fatty acid metabolism did not increase in KO mice, that of genes related to glucose utilization compensatorily increased in KO mice. The metabolomic analysis of cardiac tissues revealed that the myocardial concentrations of ATP and phosphocreatine were maintained, even in KO mice. The concentration of 3-hydroxybutyric acid and mRNA expression of hydroxybutyrate dehydrogenase in the heart were significantly higher in KO than in WT mice. Conclusion These data suggest that high-energy phosphate might be preserved by the increased utilization of glucose and ketone bodies in CD36KO mouse hearts under conditions of deficient LCFA uptake. |
| Databáze: | OpenAIRE |
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