Serum Fetuin‐B Levels Are Elevated in Women with Metabolic Syndrome and Associated with Increased Oxidative Stress

Abstract

Previous studies on serum fetuin‐B (fetuin‐like protein IRL685) have investigated its association with T2DM; however, the reason for the variation in serum fetuin‐B and its regulatory factors in metabolic disease remain unclear. Here, we evaluated serum fetuin‐B levels in women with newly diagnosed MetS and performed multiple interventions to investigate the role of fetuin‐B in the pathogenesis of MetS. Serum fetuin‐B levels were assessed using ELISA. Bioinformatics analysis was performed to analyze fetuin‐B‐related genes and signaling pathways. Additionally, oxidative stress parameters were measured in the in vitro study. For subgroup analyses, we performed EHC, OGTT, and treatment with a GLP‐1RA to investigate the regulatory factors of serum fetuin‐B. We found that in comparison with healthy subjects, serum fetuin‐B levels were markedly increased in women with MetS. Further, serum fetuin‐B showed a positive correlation with WHR, FAT%, TG, FBG, HbA1c, FIns, HOMA‐IR, VAI, and LAP. Bioinformatics analysis revealed that most fetuin‐B‐related core genes were involved in cholesterol metabolism and fat decomposition. Consistent with this finding, multivariate regression analysis showed that triglyceride content and WHR were independently associated with serum fetuin‐B. We also observed that serum fetuin‐B levels were markedly elevated in healthy subjects after glucose loading and in women with MetS during EHC. In vitro , overexpression of fetuin‐B promoted oxidative stress in HepG2 cell. After 6 months of treatment with a GLP‐1RA, serum fetuin‐B levels in women with MetS decreased following an improvement in metabolism and insulin sensitivity. Therefore, serum fetuin‐B is associated with MetS, which may serve as a biomarker of oxidative stress. This trial is registered with ChiCTR-OCC-11001422 .