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Article

Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease

1
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Department of Respiratory Medicine, P.O. Box 616, 6200 MD Maastricht, The Netherlands
2
APC Microbiome Ireland & Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 YT20 Cork, Ireland
3
APC Microbiome Ireland & Department of Anatomy and Neuroscience, University College Cork, T12 YT20 Cork, Ireland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(7), 915; https://doi.org/10.3390/jcm8070915
Received: 29 April 2019 / Revised: 20 June 2019 / Accepted: 24 June 2019 / Published: 26 June 2019
(This article belongs to the Section Clinical Neurology)
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. View Full-Text
Keywords: chronic obstructive pulmonary disease (COPD); skeletal muscle; mental health chronic obstructive pulmonary disease (COPD); skeletal muscle; mental health
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MDPI and ACS Style

Gosker, H.R.; Clarke, G.; de Theije, C.C.; Cryan, J.F.; Schols, A.M.W.J. Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease. J. Clin. Med. 2019, 8, 915. https://doi.org/10.3390/jcm8070915

AMA Style

Gosker HR, Clarke G, de Theije CC, Cryan JF, Schols AMWJ. Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease. Journal of Clinical Medicine. 2019; 8(7):915. https://doi.org/10.3390/jcm8070915

Chicago/Turabian Style

Gosker, Harry R., Gerard Clarke, Chiel C. de Theije, John F. Cryan, and Annemie M.W.J. Schols. 2019. "Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease" Journal of Clinical Medicine 8, no. 7: 915. https://doi.org/10.3390/jcm8070915

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