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Cited by 17Tryptophan and brain disordersChronic Obstructive Pulmonary Disease (COPD) ResearchMuscle Physiology and Disorders

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

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Gosker, Harry R., Clarke, Gerard, de Theije, Chiel C., Cryan, John F., Schols, Annemie M. W. J.·2019·Journal of Clinical Medicine
DOI 10.3390/jcm8070915PMC PMC6678819
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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.

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  • A recent study evidenced elevated circulating kynurenine levels in COPD patients, as well as reduced muscle levels of kynurenine aminotransferases; this dysregulated kynurenine clearance was attributed to impaired PGC1α signaling.

    “Finally, a recent study evidenced elevated circulating kynurenine levels in COPD patients, as well as reduced muscle levels of kynurenine aminotransferases; this dysregulated kynurenine clearance was attributed to impaired PGC1α signaling [145].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [145]

    The Results report higher plasma kynurenine and lower muscle KAT4 expression in COPD, but KAT1 and KAT3 were unchanged and KAT2 protein was higher—not a general reduction in kynurenine aminotransferases. The Conclusions suggest impaired muscle PGC1α signaling might be involved; the Discussion says its role in regulating KAT4 remains to be established, so the proposed mechanism is not demonstrated. (LLM, conf=0.90)

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Authors
Gosker, H. R., Clarke, G., de Theije, C. C., Cryan, J. F., & Schols, A. M. W. J.
Affiliations
  • Maastricht University Medical Centre (NL)
  • University College Cork (IE)
  • 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
Corresponding author
Gosker, Harry R.
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2019-06-26
Volume
8
Issue
7
Pages
915
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm8070915
PMC
PMC6678819
OpenAlex
W2953793753
Cited by
17
References
3
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by)
  • Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
JPI HDHL project “Ambrosiac” by ZonMW (529051006)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
chronic obstructive pulmonary disease, kynurenine metabolism, skeletal muscle, PPARγ coactivator-1α, cognitive impairment, depression, exercise training, dietary modulation

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