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; 20ppm in feed) or Reporcin (recombinant growth hormone; GH; 10mg/48hours 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.

Citation

Brown, D. M., Williams, H., Ryan, K., Wilson, T., Daniel, Z. C., Mareko, M. H. D., Emes, R. D., Harris, D. W., Wattis, J. A., Dryden, I. L., Hodgman, T. C., Brameld, J. M., & Parr, T. (2016). Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth. Scientific Reports, 6(1), https://doi.org/10.1038/srep28693

• 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
• Contract Date: Aug 1, 2016