title: Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.
abstract: We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth.
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Brown
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.|School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: K J P
authors.initials: KJ
authors.lastname: Ryan
authors.affiliation: VMRD Global Therapeutics Research, Zoetis, Kalamazoo, MI, 49007, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Wilson
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: Z C T R
authors.initials: ZC
authors.lastname: Daniel
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: M H D
authors.initials: MH
authors.lastname: Mareko
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Emes
authors.affiliation: VMRD Global Therapeutics Research, Zoetis, Kalamazoo, MI, 49007, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Harris
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.affiliation: School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: J A D
authors.initials: JA
authors.lastname: Wattis
authors.affiliation: School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: I L
authors.initials: IL
authors.lastname: Dryden
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: T C
authors.initials: TC
authors.lastname: Hodgman
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Brameld
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
authors.forename: T
authors.initials: T
authors.lastname: Parr
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development*; D010627:Phenethylamines / Q000494:pharmacology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism*; D012694:Serine / Q000096:biosynthesis*; D013552:Swine
chemical_list: D045930:Anabolic Agents; D024101:Mitochondrial Proteins; D010627:Phenethylamines; D012694:Serine; C060897:ractopamine; D019764:Phosphoenolpyruvate Carboxykinase (ATP)