Advertisement

Overnight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis

  • Rita J. Louard
    Affiliations
    Department of Internal Medicine, Section of Endocrinology and Metabolism, and the General Clinical Research Center, Yale University School of Medicine, New Haven, CT, USA

    Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, VA, USA
    Search for articles by this author
  • Eugene J. Barrett
    Affiliations
    Department of Internal Medicine, Section of Endocrinology and Metabolism, and the General Clinical Research Center, Yale University School of Medicine, New Haven, CT, USA

    Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, VA, USA
    Search for articles by this author
  • Robert A. Gelfand
    Correspondence
    Address reprint requests to Robert A. Gelfand, MD, Pfizer Central Research, Eastern Point Road, Groton, CT 06340.
    Affiliations
    Department of Internal Medicine, Section of Endocrinology and Metabolism, and the General Clinical Research Center, Yale University School of Medicine, New Haven, CT, USA

    Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, VA, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Short-term (3 to 4 hours) infusion of branched-chain amino acids (BCAA) has been shown to suppress muscle protein breakdown. Whether these effects are sustained with chronic elevations of BCAA is not known. In the present study, we examined the effect of an overnight (16-hour) systemic BCAA infusion on whole-body and skeletal muscle amino acid metabolism, as assessed by simultaneously measured 3H-phenylalanine and 14C-leucine kinetics in eight normal volunteers; 10 overnight-fasted subjects studied during a 4-hour saline infusion served as controls. Overnight BCAA infusion increased plasma BCAA concentrations by fivefold to eightfold, and this was associated with a 20% to 60% decline in arterial concentrations of other amino acids. For Phe, this decline was mediated by a reduction in the systemic rate of appearance ([Ra] 0.38 ± 0.03 v 0.60 ± 0.01 μmol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu Ra, calculated more indirectly as the difference between the total Leu Ra and the unlabeled Leu infusion rate, did not differ between groups. In the forearm, overnight BCAA infusion resulted in a diminished net release of Phe (−3 ± 2 v −18 ± 4 [saline] nmol/min/100 mL, P < .02), and BCAA balance became markedly positive (751 ± 93 v −75 ± 30, P < .001). The diminished net forearm Phe release was accounted for by a decrease in local Phe Ra (P < .02). As with the systemic endogenous Leu Ra, forearm Leu Ra was not reproducibly affected by infused BCAA. These findings suggest a need for caution in the application of amino acid tracer kinetic methods when tracer and unlabeled tracee are infused simultaneously. In conclusion, overnight BCAA infusion caused a sustained decline in most plasma amino acids and in net forearm release of Phe, effects attributable to a sustained suppression of whole-body and muscle proteolysis.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Eriksson S
        • Hagenfeldt L
        • Wahren J
        A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man.
        Clin Sci. 1981; 60: 95-100
        • Hagenfeldt L
        • Eriksson S
        • Wahren J
        Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects.
        Clin Sci. 1980; 59: 173-181
        • Louard RJ
        • Barrett EJ
        • Gelfand RA
        Effect of infused branched chain amino acids on muscle and whole-body amino acid metabolism in man.
        Clin Sci. 1990; 79: 457-466
        • Nair KS
        • Schwartz RS
        • Welle SL
        Evidence for regulatory role of leucine on in vivo protein metabolism in humans.
        Clin Res. 1989; 37 (abstr): 333A
        • Schwenk WF
        • Haymond MW
        Effects of leucine, isoleucine, or threonine infusion on leucine metabolism in humans.
        Am J Physiol. 1987; 253: E428-E434
        • Sherwin RS
        Effect of starvation on the turnover and metabolic response to leucine.
        J Clin Invest. 1978; 61: 1471-1481
        • Fukagawa NK
        • Minaker KL
        • Good WR
        • et al.
        Acute effects of insulin-like growth factor I (IGF) on leucine kinetics in healthy men.
        Diabetes. 1990; 39 (abstr): 3A
        • Fukagawa NK
        • Minaker KL
        • Rowe JW
        • et al.
        Insulin-mediated reduction of whole body protein breakdown.
        in: Dose-response effects on leucine metabolism in postabsorptive man. ed 3. J Clin Invest. 76. 1985: 2306-2311
        • Gelfand RA
        • Barrett EJ
        Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.
        J Clin Invest. 1987; 80: 1-6
        • Miles JM
        • Nissen SL
        • Gerich JE
        • et al.
        Effects of epinephrine infusion on leucine and alanine kinetics in humans.
        Am J Physiol. 1984; 247: E166-E172
        • Fryburg DA
        • Barrett EJ
        • Louard RJ
        • et al.
        Effect of starvation on human muscle protein metabolism and its response to insulin.
        Am J Physiol. 1990; 259: E477-E482
        • Nissen SL
        • Van Huysen C
        • Haymond MW
        Measurement of plasma α-ketoisocaproate concentrations and specific radioactivity of high-performance liquid chromatography.
        Anal Biochem. 1981; 110: 389-392
        • Nissen SL
        • Van Huysen C
        • Haymond MW
        Measurement of branched-chain amino acids and branched-chain ketoacids in plasma by high-performance liquid chromatography.
        J Chromatogr. 1982; 232: 170-175
        • Matthews DE
        • Schwarz HP
        • Yang RD
        • et al.
        Relationship of plasma leucine and α-ketoisocaproate during l-[1-13C]leucine infusion in man: A method for measuring human intracellular leucine tracer enrichment.
        Metabolism. 1982; 31: 1105-1111
        • Castellino P
        • Luzi L
        • Simonson DC
        • et al.
        Effect of insulin and plasma amino acid concentrations on leucine metabolism in man: Role of substrate availability on estimates of whole body protein synthesis.
        J Clin Invest. 1987; 80: 1784-1793
        • Fryburg DA
        • Gelfand RA
        • Barrett EJ
        Growth hormone acutely stimulates forearm muscle protein synthesis in normal man.
        Am J Physiol. 1991; 260: E499-E504
        • Bier DM
        • Matthews DE
        • Young VR
        Interpretation of amino acid kinetic studies in the context of whole-body protein metabolism.
        in: Garrow JS Halliday D Substrate and Energy Metabolism in Man. Libbey, London, UK1985: 27-36
        • Bell PM
        • Firth RG
        • Rizza RA
        Assessment of insulin action in insulin-dependent diabetes mellitus using [6-14C]glucose, [3-3H]glucose, and [2-3H]glucose: Differences in the apparent pattern of insulin resistance depending on the isotope used.
        J Clin Invest. 1986; 78: 1479-1486
        • McMahon MM
        • Schwenk WF
        • Haymond MW
        • et al.
        Underestimation of glucose turnover measured with [6-3H]- and [6,6,-2H2]- but not [6-14C]glucose during hyperinsulinemia in humans.
        Diabetes. 1989; 38: 97-107