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健康受试者以及肥胖、抑郁和慢性阻塞性肺疾病患者体内的犬尿氨酸途径

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

作者信息

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

机构信息

Department of Research, Innlandet Hospital Trust, N-2381 Brumunddal, Norway.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.

出版信息

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

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.

摘要

背景

在多种疾病中均观察到通过犬尿氨酸途径(KP)的色氨酸代谢变化,且这些变化与病理生理偏差相关。

方法

本研究回顾性比较了参与四项临床研究的健康受试者(108名)与肥胖受试者(141名)、抑郁症患者(49名)和慢性阻塞性肺疾病(COPD)患者(22名)血清中的KP,并探讨了KP代谢产物变化的预测因素。

结果

与健康组相比,疾病组中犬尿氨酸、喹啉酸(QA)、犬尿氨酸/色氨酸比值和QA/黄尿酸比值升高,犬尿酸/QA比值降低,KP上调。与肥胖组和COPD组相比,抑郁症组中的色氨酸和黄尿酸上调。协变量体重指数、吸烟、糖尿病和C反应蛋白解释了健康组与肥胖组之间的显著差异,但不能解释健康组与抑郁症组和COPD组之间的差异,这表明不同的病理生理状况导致了KP的相同变化。

结论

与健康组相比,疾病组中的KP显著上调,且疾病组之间存在显著差异。不同的病理生理异常似乎导致了KP的相同偏差。

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