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

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...

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Main Authors: 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
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Published: Nature Publishing Group 2016
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Online Access:https://eprints.nottingham.ac.uk/34208/
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author 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
author_facet 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
author_sort Brown, David M.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-342082024-08-15T15:19:19Z https://eprints.nottingham.ac.uk/34208/ 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 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. Nature Publishing Group 2016-06-28 Article PeerReviewed 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. and Parr, Tim (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 . ISSN 2045-2322 Pck2; PHGDH; Beta-adrenergic agonist; Growth hormone; Porcine; Muscle http://www.nature.com/articles/srep28693 doi:10.1038/srep28693 doi:10.1038/srep28693
spellingShingle Pck2; PHGDH; Beta-adrenergic agonist; Growth hormone; Porcine; Muscle
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
Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title_full Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title_fullStr Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title_full_unstemmed Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title_short Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
title_sort mitochondrial phosphoenolpyruvate carboxykinase (pepck-m) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth
topic Pck2; PHGDH; Beta-adrenergic agonist; Growth hormone; Porcine; Muscle
url https://eprints.nottingham.ac.uk/34208/
https://eprints.nottingham.ac.uk/34208/
https://eprints.nottingham.ac.uk/34208/