Impaired skeletal muscle kynurenine metabolism in patients with chronic obstructive pulmonary disease
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Published version
Date
2019-06-26
Authors
Gosker, Harry R.
Clarke, Gerard
de Theije, Chiel C.
Cryan, John F.
Schols, Annemie M. W. J.
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Published Version
Abstract
Background: Loss of peripheral muscle oxidative phenotype, cognitive impairment, and depression are well-recognized systemic manifestations of chronic obstructive pulmonary disease (COPD). Kynurenine (KYN), known to be associated with disturbed mental health, can be metabolized in muscle by kynurenine aminotransferases (KAT) 1–4. These KATs are regulated by peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC1α). We hypothesize that impaired PGC1α signaling in COPD is associated with reduced muscle KAT expression and increased KYN plasma levels. Methods: Retrospective collected and metabolically phenotyped muscle tissue and blood obtained from 29 well-characterized COPD patients and 15 healthy controls were analyzed. KYN was measured in plasma and KAT1–4 expression and major constituents of PGC1α signaling were assessed in quadriceps muscle biopsies. Results: Circulating KYN levels were increased in COPD. Furthermore, both gene and protein expression levels of KAT4 were reduced in muscle tissue from COPD patients. Finally, in the whole group (even when controlled for airflow obstruction) and in each subgroup separately, KAT4 gene expression correlated significantly with constituents of the PGC1α signaling pathway. Conclusions: These data support our hypothesis that KYN plasma levels are elevated in COPD through impaired KYN clearance in muscle. Our findings show a pathway via which exercise training and/or nutritional modulation may improve physical and mental health in COPD patients.
Description
Keywords
Chronic obstructive pulmonary disease (COPD) , Skeletal muscle , Mental health
Citation
Gosker, H.R., Clarke, G., de Theije, C.C., Cryan, J.F. and Schols, A.M., 2019. Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease. Journal of Clinical Medicine, 8(7), (915). DOI:10.3390/jcm8070915