A new leptin-mediated mechanism for stimulating fatty acid oxidation
| Autor: | Swati S. Jain, Iman Momken, Jan F. C. Glatz, Joost J. F. P. Luiken, Miranda Nabben, Adrian Chabowski, Ellen Dirkx, Jay T. McFarlan, Arend Bonen |
|---|---|
| Přispěvatelé: | RS: CARIM - R2.07 - Gene regulation, Cardiologie, Moleculaire Genetica, RS: CARIM - R2.06 - Intermediate cardiac metabolism, Unité de biologie intégrative des adaptations à l'exercice (UBIAE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, Maastricht University [Maastricht], University of Guelph, Medical University of Białystok (MUB) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD36 Antigens Leptin [SDV]Life Sciences [q-bio] Glucose uptake CD36 Oleic Acids animal cell AMP-Activated Protein Kinases Biochemistry Western blotting Mice Sarcolemma CD36 antigen Myocyte rat animal genetics Myocytes Cardiac Phosphorylation Beta oxidation sulfo-N-succinimidyl oleate fatty acid oxidation fatty acid transport chemistry.chemical_classification Mice Knockout cardiac muscle cell biology Chemistry MEMBRANE-PROTEINS Fatty Acids ACTIVATED PROTEIN-KINASE hydroxymethylglutaryl coenzyme A reductase kinase Skeletal succinimide derivative Protein Transport medicine.anatomical_structure priority journal enzyme active site Muscle SKELETAL-MUSCLE LIPID-ACCUMULATION Cardiac Oxidation-Reduction Vidarabine medicine.medical_specialty Knockout Succinimides CELLULAR REDISTRIBUTION RAT CARDIAC MYOCYTES OB/OB MICE Article Fatty acid-binding protein Cell Line 03 medical and health sciences male Internal medicine medicine Animals controlled study skeletal muscle Antigens Muscle Skeletal Molecular Biology mouse Myocytes Cd36 protein nonhuman GLUCOSE-UPTAKE Skeletal muscle Fatty acid AMPK enzyme activation Cell Biology TRANSPORT protein phosphorylation Rats 030104 developmental biology Endocrinology oleic acid drug effects PLASMA-MEMBRANE biology.protein fatty acid knockout mouse cell membrane metabolism oxidation reduction reaction energy yield |
| Zdroj: | Biochemical Journal, 474(1), 149-162. Portland Press Ltd. Biochemical Journal Biochemical Journal, 2017, 474 (1), pp.149-162. ⟨10.1042/BCJ20160804⟩ |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | International audience; Leptin stimulates fatty acid oxidation in muscle and heart; but, the mechanism by which these tissues provide additional intracellular fatty acids for their oxidation remains unknown. We examined, in isolated muscle and cardiac myocytes, whether leptin, via AMP-activated protein kinase (AMPK) activation, stimulated fatty acid translocase (FAT/CD36)-mediated fatty acid uptake to enhance fatty acid oxidation. In both mouse skeletal muscle and rat cardiomyocytes, leptin increased fatty acid oxidation, an effect that was blocked when AMPK phosphorylation was inhibited by adenine 9-β-D-arabinofuranoside or Compound C. In wild-type mice, leptin induced the translocation of FAT/CD36 to the plasma membrane and increased fatty acid uptake into giant sarcolemmal vesicles and into cardiomyocytes. In muscles of FAT/CD36-KO mice, and in cardiomyocytes in which cell surface FAT/CD36 action was blocked by sulfo-N-succinimidyl oleate, the leptin-stimulated influx of fatty acids was inhibited; concomitantly, the normal leptin-stimulated increase in fatty acid oxidation was also prevented, despite the normal leptin-induced increase in AMPK phosphorylation. Conversely, in muscle of AMPK kinase-dead mice, leptin failed to induce the translocation of FAT/CD36, along with a failure to stimulate fatty acid uptake and oxidation. Similarly, when siRNA was used to reduce AMPK in HL-1 cardiomyocytes, leptin failed to induce the translocation of FAT/CD36. Our studies have revealed a novel mechanism of leptin-induced fatty acid oxidation in muscle tissue; namely, this process is dependent on the activation of AMPK to induce the translocation of FAT/CD36 to the plasma membrane, thereby stimulating fatty acid uptake. Without increasing this leptin-stimulated, FAT/CD36-dependent fatty acid uptake process, leptin-stimulated AMPK phosphorylation does not enhance fatty acid oxidation. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. |
| Databáze: | OpenAIRE |
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