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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-\u03b2-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.<\/jats:p>","DOI":"10.1042\/bcj20160804","type":"journal-article","created":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T12:04:07Z","timestamp":1478693047000},"page":"149-162","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A new leptin-mediated mechanism for stimulating fatty acid oxidation: a pivotal role for sarcolemmal FAT\/CD36"],"prefix":"10.1042","volume":"474","author":[{"given":"Iman","family":"Momken","sequence":"first","affiliation":[{"name":"Integrated Biology Unit for Adaptations to Exercise (UBIAE-EA7362), University of Evry Val Essonne, Boulevard Fran\u00e7ois Mitterrand, 91025 Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Chabowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Dirkx","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Maastricht University, 6200-MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Nabben","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Maastricht University, 6200-MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati S.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay T.","family":"McFarlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan F.C.","family":"Glatz","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Maastricht University, 6200-MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost J.F.P.","family":"Luiken","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Maastricht University, 6200-MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend","family":"Bonen","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,12,22]]},"reference":[{"key":"2021112216375289200_BCJ-2016-0804C1","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.2337\/diab.46.8.1360","article-title":"Leptin directly alters lipid partitioning in skeletal muscle","volume":"46","author":"Muoio","year":"1997","journal-title":"Diabetes"},{"issue":"5 Pt 1","key":"2021112216375289200_BCJ-2016-0804C2","doi-asserted-by":"crossref","first-page":"E913","DOI":"10.1152\/ajpendo.1999.276.5.E913","article-title":"Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob\/ob mice","volume":"276","author":"Muoio","year":"1999","journal-title":"Am. 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