title: Leucine stimulates PPARβ/δ-dependent mitochondrial biogenesis and oxidative metabolism with enhanced GLUT4 content and glucose uptake in myotubes.
abstract: Leucine stimulates anabolic and catabolic processes in skeletal muscle, however little is known about the effects of leucine on peroxisome proliferator-activated receptor (PPAR) activity. This work characterized the effects of 24-h leucine treatment on metabolic parameters and protein expression in cultured myotubes. Leucine significantly increased PPARβ/δ expression as well as markers of mitochondrial biogenesis, leading to significantly increased mitochondrial content and oxidative metabolism in a PPARβ/δ-dependent manner. However, leucine-treated cells did not display significant alterations in uncoupling protein expression or oxygen consumed per relative mitochondrial content suggesting leucine-mediated increases in oxidative metabolism are a function of increased mitochondrial content and not altered mitochondrial efficiency. Leucine treatment also increased GLUT4 content and glucose uptake as well as PPARγ and FAS expression leading to increased total lipid content. Leucine appears to activate PPAR activity leading to increased mitochondrial biogenesis and elevated substrate oxidation, while simultaneously promoting substrate/lipid storage and protein synthesis.
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC, 27268, USA. Electronic address: schnuj12@highpoint.edu.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Schnuck
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC, 27268, USA. Electronic address: ksunderl@highpoint.edu.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Sunderland
authors.affiliation: School of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. Electronic address: ngannon@mcw.edu.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Gannon
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC, 27268, USA. Electronic address: mkuennen@highpoint.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Kuennen
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC, 27268, USA. Electronic address: rvaughan@highpoint.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Vaughan
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D015151:Immunoblotting; D007930:Leucine / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000032:analysis; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D001678:Organelle Biogenesis; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D047494:PPAR delta / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D008055:Lipids; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta; D007930:Leucine; D005947:Glucose
keywords: Mitochondrial biogenesis; PGC-1α; PPARα; PPARβ/δ; PPARγ