The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease

Per G Farup; Håvard Hamarsland; Knut Sindre Mølmen; Stian Ellefsen; Knut Hestad

doi:10.3390/ph16030351

The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease

Pharmaceuticals (Basel). 2023 Feb 25;16(3):351. doi: 10.3390/ph16030351.

Authors

Per G Farup^{1

2}, Håvard Hamarsland³, Knut Sindre Mølmen³, Stian Ellefsen^{1

3}, Knut Hestad^{1

4}

Affiliations

¹ Department of Research, Innlandet Hospital Trust, N-2381 Brumunddal, Norway.
² Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
³ Section for Health and Exercise Physiology, Faculty of Social and Health Sciences, Inland Norway University of Applied Sciences, N-2624 Lillehammer, Norway.
⁴ Department of Health and Nursing Science, Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2418 Elverum, Norway.

Abstract

Background: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations.

Methods: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites.

Results: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP.

Conclusions: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.

Keywords: chronic obstructive pulmonary disease; depression; inflammation; kynurenine pathway; obesity.

Grants and funding

This research was funded by Innlandet Hospital Trust, Brumunddal, Norway; Inland Norway University of Applied Sciences, Lillehammer, Norway; and Regional Research Fund Inland, Norway (grant number 298419, S.E.)