dc.contributor.author | Wilkinson, DJ | |
dc.contributor.author | Hossain, T | |
dc.contributor.author | Hill, DS | |
dc.contributor.author | Phillips, BE | |
dc.contributor.author | Crossland, H | |
dc.contributor.author | Williams, J | |
dc.contributor.author | Loughna, P | |
dc.contributor.author | Churchward-Venne, TA | |
dc.contributor.author | Breen, L | |
dc.contributor.author | Phillips, SM | |
dc.contributor.author | Etheridge, T | |
dc.contributor.author | Rathmacher, JA | |
dc.contributor.author | Smith, K | |
dc.contributor.author | Szewczyk, NJ | |
dc.contributor.author | Atherton, PJ | |
dc.date.accessioned | 2017-03-14T10:37:11Z | |
dc.date.issued | 2013-06-01 | |
dc.description.abstract | Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu. | en_GB |
dc.description.sponsorship | Metabolic Technologies Inc. supplied the HMB on a collaborative basis and undertook the HMB plasma and intramuscular analyses, but were blinded to the sample identities. P.J.A. was a designated RCUK Fellow. Work completed in the UK was funded by grants from the Royal Society (RG2010/R2) and the University of Nottingham. D.H., H.C. and N.J.S. were supported by the US NIH (AR-054342). D.J.W. and N.J.S. were supported by the MRC (G0801271). Portions of work completed by T.A.C.-V. and L.B. were supported by a grant from the Canadian National Science and Engineering Research Council (NSERC) of Canada to S.M.P. We gratefully acknowledge the work of T. Rerecich in assisting with lab analyses. | en_GB |
dc.identifier.citation | Vol. 591, Iss. 11, pp. 2911 - 2923 | en_GB |
dc.identifier.doi | 10.1113/jphysiol.2013.253203 | |
dc.identifier.other | jphysiol.2013.253203 | |
dc.identifier.uri | http://hdl.handle.net/10871/26552 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/23551944 | en_GB |
dc.rights | © 2013 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | Administration, Oral | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Leucine | en_GB |
dc.subject | Male | en_GB |
dc.subject | Muscle, Skeletal | en_GB |
dc.subject | Protein Biosynthesis | en_GB |
dc.subject | Proteolysis | en_GB |
dc.subject | Tissue Distribution | en_GB |
dc.subject | Valerates | en_GB |
dc.subject | Young Adult | en_GB |
dc.title | Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-03-14T10:37:11Z | |
dc.identifier.issn | 0022-3751 | |
exeter.place-of-publication | England | en_GB |
dc.description | Published | en_GB |
dc.description | Journal Article | en_GB |
dc.description | This is the final version of the article. Available from Wiley via the DOI in this record. | en_GB |
dc.identifier.eissn | 1469-7793 | |
dc.identifier.journal | Journal of Physiology | en_GB |