Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

Brown, David M.; Williams, Hannah; Ryan, K.J.P.; Wilson, T.L.; Daniel, Zoe C.T.R.; Mareko, M. H. D.; Emes, Richard D.; Harris, D. W.; Wattis, Jonathan A.D.; Dryden, Ian L.; Hodgman, T. C.; Brameld, John M.; Parr, Tim

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.

• Journal Article Type: Article
• Acceptance Date: Jun 8, 2016
• Online Publication Date: Jun 28, 2016
• Publication Date: Jun 28, 2016
• Deposit Date: Aug 1, 2016
• Publicly Available Date: Aug 1, 2016
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• DOI: https://doi.org/10.1038/srep28693
• Keywords: Pck2; PHGDH; Beta-adrenergic agonist; Growth hormone; Porcine; Muscle
• Public URL: https://nottingham-repository.worktribe.com/output/793169
• Publisher URL: http://www.nature.com/articles/srep28693