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

• Published in: American Journal of Physiology: Cell Physiology 2022-01, Vol.322 (1), p.C49-C62
• Main Authors: Jonsson, William O, Ponette, Jonathan, Horwath, Oscar, Rydenstam, Tomas, Söderlund, Karin, Ekblom, Björn, Azzolini, Michele, Ruas, Jorge L, Blomstrand, Eva
• Format: Article
• Language: English
• Subjects: Adult; Amino acids; Amino Acids, Branched-Chain - administration & dosage; Biopsy; Exercise - physiology; Female; Humans; Kynurenic acid; Kynurenine - blood; Kynurenine - metabolism; Leg; Male; Medicin och hälsovetenskap; Medicin/Teknik; Medicine/Technology; Metabolism; Mitochondria; mRNA; muscle; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; PGC-1α; Placebos; Plasma; Plasma levels; tryptophan; Young Adult
• ISSN: 0363-6143; 1522-1563; 1522-1563
• DOI: 10.1152/ajpcell.00285.2021

Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ∼70% of 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 ( < 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% ( < 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 ( < 0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% ( < 0.01) during exercise and recovery, whereas the level remained unchanged with placebo. Exercise induced a three- to fourfold increase ( < 0.05) in muscle content of PGC-1α1 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.