Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy

Charles H. Lang, Anne Pruznak, Maithili Navaratnarajah, Kristina A. Rankine, Gina Deiter, Hugues Magne, Elizabeth A. Offord, Denis Breuillé

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Muscle disuse atrophy is observed routinely in patients recovering from traumatic injury and can be either generalized resulting from extended bed rest or localized resulting from single-limb immobilization. The present study addressed the hypothesis that a diet containing 5% α-hydroxyisocaproic acid (α-HICA), a leucine (Leu) metabolite, will slow the loss and/or improve recovery of muscle mass in response to disuse. Adult 14-wk-old male Wistar rats were provided a control diet or an isonitrogenous isocaloric diet containing either 5% α-HICA or Leu. Disuse atrophy was produced by unilateral hindlimb immobilization ("casting") for 7 days and the contralateral muscle used as control. Rats were also casted for 7 days and permitted to recover for 7 or 14 days. Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. Although neither α-HICA nor Leu prevented the casting-induced muscle atrophy, the decreased muscle protein synthesis was not observed in α-HICA-treated rats. Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. After 14 days of recovery, muscle mass had returned to control values only in the rats fed α-HICA, and this was associated with a sustained increase in protein synthesis and phosphorylation of S6K1 and 4E-BP1 of previously immobilized muscle. Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. These data suggest that whereas α-HICA does not slow the loss of muscle produced by disuse, it does speed recovery at least in part by maintaining an increased rate of protein synthesis.

Original languageEnglish (US)
Pages (from-to)E416-E428
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number3
DOIs
StatePublished - Aug 1 2013

Fingerprint

Immobilization
Atrophy
Leucine
Proteasome Endopeptidase Complex
Muscles
Acids
Atrophic Muscular Disorders
Muscular Atrophy
Diet
Phosphorylation
Hindlimb Suspension
Therapeutics
Messenger RNA
Bed Rest
Proteins
Muscle Proteins
Wistar Rats
Extremities
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Lang, Charles H. ; Pruznak, Anne ; Navaratnarajah, Maithili ; Rankine, Kristina A. ; Deiter, Gina ; Magne, Hugues ; Offord, Elizabeth A. ; Breuillé, Denis. / Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 305, No. 3. pp. E416-E428.
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Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy. / Lang, Charles H.; Pruznak, Anne; Navaratnarajah, Maithili; Rankine, Kristina A.; Deiter, Gina; Magne, Hugues; Offord, Elizabeth A.; Breuillé, Denis.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 305, No. 3, 01.08.2013, p. E416-E428.

Research output: Contribution to journalArticle

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AU - Lang, Charles H.

AU - Pruznak, Anne

AU - Navaratnarajah, Maithili

AU - Rankine, Kristina A.

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AU - Offord, Elizabeth A.

AU - Breuillé, Denis

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N2 - Muscle disuse atrophy is observed routinely in patients recovering from traumatic injury and can be either generalized resulting from extended bed rest or localized resulting from single-limb immobilization. The present study addressed the hypothesis that a diet containing 5% α-hydroxyisocaproic acid (α-HICA), a leucine (Leu) metabolite, will slow the loss and/or improve recovery of muscle mass in response to disuse. Adult 14-wk-old male Wistar rats were provided a control diet or an isonitrogenous isocaloric diet containing either 5% α-HICA or Leu. Disuse atrophy was produced by unilateral hindlimb immobilization ("casting") for 7 days and the contralateral muscle used as control. Rats were also casted for 7 days and permitted to recover for 7 or 14 days. Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. Although neither α-HICA nor Leu prevented the casting-induced muscle atrophy, the decreased muscle protein synthesis was not observed in α-HICA-treated rats. Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. After 14 days of recovery, muscle mass had returned to control values only in the rats fed α-HICA, and this was associated with a sustained increase in protein synthesis and phosphorylation of S6K1 and 4E-BP1 of previously immobilized muscle. Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. These data suggest that whereas α-HICA does not slow the loss of muscle produced by disuse, it does speed recovery at least in part by maintaining an increased rate of protein synthesis.

AB - Muscle disuse atrophy is observed routinely in patients recovering from traumatic injury and can be either generalized resulting from extended bed rest or localized resulting from single-limb immobilization. The present study addressed the hypothesis that a diet containing 5% α-hydroxyisocaproic acid (α-HICA), a leucine (Leu) metabolite, will slow the loss and/or improve recovery of muscle mass in response to disuse. Adult 14-wk-old male Wistar rats were provided a control diet or an isonitrogenous isocaloric diet containing either 5% α-HICA or Leu. Disuse atrophy was produced by unilateral hindlimb immobilization ("casting") for 7 days and the contralateral muscle used as control. Rats were also casted for 7 days and permitted to recover for 7 or 14 days. Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. Although neither α-HICA nor Leu prevented the casting-induced muscle atrophy, the decreased muscle protein synthesis was not observed in α-HICA-treated rats. Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. After 14 days of recovery, muscle mass had returned to control values only in the rats fed α-HICA, and this was associated with a sustained increase in protein synthesis and phosphorylation of S6K1 and 4E-BP1 of previously immobilized muscle. Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. These data suggest that whereas α-HICA does not slow the loss of muscle produced by disuse, it does speed recovery at least in part by maintaining an increased rate of protein synthesis.

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