Impaired skeletal muscle kynurenine metabolism in patients with chronic obstructive pulmonary disease

Gosker, Harry R.; Clarke, Gerard; de Theije, Chiel C.; Cryan, John F.; Schols, Annemie M. W. J.

Impaired skeletal muscle kynurenine metabolism in patients with chronic obstructive pulmonary disease

dc.contributor.author	Gosker, Harry R.
dc.contributor.author	Clarke, Gerard
dc.contributor.author	de Theije, Chiel C.
dc.contributor.author	Cryan, John F.
dc.contributor.author	Schols, Annemie M. W. J.
dc.contributor.funder	ZonMw	en
dc.date.accessioned	2019-11-01T08:03:58Z
dc.date.available	2019-11-01T08:03:58Z
dc.date.issued	2019-06-26
dc.description.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.	en
dc.description.sponsorship	ZonMW (project number 529051006)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	915	en
dc.identifier.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	en
dc.identifier.doi	10.3390/jcm8070915	en
dc.identifier.eissn	2077-0383
dc.identifier.endpage	7	en
dc.identifier.issued	7	en
dc.identifier.journaltitle	Journal of Clinical Medicine	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/8938
dc.identifier.volume	8	en
dc.language.iso	en	en
dc.publisher	MDPI	en
dc.relation.project	info:eu-repo/grantAgreement/RCUK/MRC/MR/N029488/1/GB/AMBROSIAC - A Menu for Brain Responses Opposing Stress-Induced Alterations in Cognition/	en
dc.relation.project	info:eu-repo/grantAgreement/EC/H2020::CSA/696300/EU/The second coordination and support action for the JPI Healthy Diet for a Healthy Life/CSA JPI HDHL 2.0	en
dc.relation.uri	https://www.mdpi.com/2077-0383/8/7/915
dc.rights	© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	Chronic obstructive pulmonary disease (COPD)	en
dc.subject	Skeletal muscle	en
dc.subject	Mental health	en
dc.title	Impaired skeletal muscle kynurenine metabolism in patients with chronic obstructive pulmonary disease	en
dc.type	Article (peer-reviewed)	en