Xanthine oxidoreductase activity in MASLD: links to lipid metabolism, oxidative stress, and inflammation

TL;DR

This study finds that xanthine oxidoreductase activity is elevated in people with MASLD and is linked to changes in lipid metabolism, oxidative stress, and inflammation.

Contribution

The study identifies specific metabolites and their associations with XOR activity, oxidative stress, and inflammation in MASLD patients.

Findings

MASLD patients had significantly higher xanthine oxidoreductase activity compared to healthy controls.

100 metabolites were found to be differentially expressed in MASLD patients, with 44 specifically linked to XOR activity.

Altered metabolites were correlated with lipid profiles, oxidative stress markers, and inflammatory factors.

Abstract

To evaluate the differences in xanthine oxidoreductase (XOR) activity, metabolomic profiles, markers of oxidative stress, and inflammatory factors between patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and healthy controls, as well as the correlations among these factors.

A case-control study was conducted involving 54 MASLD patients alongside 54 healthy controls who were matched for age, gender, and ethnicity. Participants underwent comprehensive blood biochemical testing, including liver function, kidney function, glucose, lipid, XOR activity, markers of oxidative stress, and inflammatory factors. Non-targeted metabolomics detection was conducted to identify alterations in the metabolites of MASLD patients.

MASLD patients showed significantly elevated levels of XOR activity, and this increase was positively correlated with significantly altered markers of oxidative stress and inflammatory factors, including increased malondialdehyde levels, tumor necrosis factor-α and interleukin-6. Metabolomic analysis revealed a unique pattern of specific metabolites, including animo acids, sphingolipids, phospholipids, and fatty acids, which were significantly altered in MASLD. A total of 100 metabolites were identified as differentially expressed between MASLD and control groups, with 44 metabolites specifically associated with XOR activity. These metabolites were significantly correlated with lipid profiles, oxidative stress indices, and inflammatory factors.

This study demonstrates significant alterations in XOR activity, lipid metabolism, oxidative stress, and inflammatory reactions in MASLD, as well as the significant association between these factors.

Figures