4.7 Article

Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 322, Issue 1, Pages C49-C62

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00285.2021

Keywords

kynurenic acid; muscle; PGC-1a; tryptophan

Funding

  1. Swedish Research Council for Sport Science (Stockholm, Sweden)
  2. Novo Nordisk Fonden

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Administration of BCAA can enhance mitochondrial biogenesis and lower plasma levels of aromatic amino acids, kynurenine, and kynurenic acid. However, BCAA did not affect muscle kynurenine levels, suggesting that kynurenine metabolism was altered in tissues other than muscle.
Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1a, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at -70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after, and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration in both plasma and muscle while causing a 30%-40% reduction (P < 0.05 vs. placebo) in levels of aromatic amino acids in both resting and exercising muscle during 3-h recovery period. The muscle concentration of kynurenine decreased by 25% (P < 0.05) during recovery, similar in both resting and exercising leg and with both supplements, although plasma concentration of kynurenine during recovery was 10% lower (P < 0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% (P < 0.01) during exercise and recovery, whereas the level remained unchanged with placebo. Exercise induced a three- to fourfold increase (P < 0.05) in muscle content of PGC-1a1 mRNA after 90 min of recovery under both conditions, whereas levels of KAT4 mRNA and protein were unaffected by exercise or supplement. In conclusion, the reduction of plasma levels of kynurenine and kynurenic acid caused by BCAA were not associated with any changes in the level of muscle kynurenine, suggesting that kynurenine metabolism was altered in tissues other than muscle.

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