A new leptin-mediated mechanism for stimulating fatty acid oxidation
| العنوان: | A new leptin-mediated mechanism for stimulating fatty acid oxidation |
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| المؤلفون: | 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 |
| المساهمون: | 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) |
| المصدر: | Biochemical Journal, 474(1), 149-162. Portland Press Ltd. Biochemical Journal Biochemical Journal, 2017, 474 (1), pp.149-162. ⟨10.1042/BCJ20160804⟩ |
| بيانات النشر: | Portland Press Ltd., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea71e192503cc2edd157c72263c31070Test https://doi.org/10.1042/BCJ20160804Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ea71e192503cc2edd157c72263c31070 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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