Fetuin B is related to cytokine/chemokine and insulin signaling in adipose tissue and plasma in humans

OBJECTIVE: Fetuin B is a steatosis-responsive hepatokine that induces glucose intolerance in mice. Recently, we found that fetuin B in white adipose tissue was positively associated with peripheral insulin resistance in mice and a small study population, possibly through a fetuin B-induced inflammatory response in adipocytes. This translational study aimed to investigate the link between plasma fetuin B and the adipose tissue transcriptome and plasma proteome in a large cohort of humans. METHODS: Continuous linear regression analysis in R was applied to investigate the link between plasma fetuin B and the adipose tissue transcriptome (n=207) and plasma proteome (n=558) in humans, after adjustment for sex, age and study centre (model 1), model 1 + BMI (model 2) and model 2 + insulin sensitivity (MATSUDA-index) (model 3). RESULTS: Plasma fetuin B was associated with >100 genes in white adipose tissue, belonging to pathways related to cytokine/chemokine signaling (models 1 and 2) and insulin signaling (all models), and with >146 plasma proteins, involved in pathways related to metabolic processes and insulin signaling (all models). CONCLUSION: Plasma fetuin B is related to adipose tissue genes and plasma proteins involved in metabolic processes and insulin signaling. Our findings provide evidence for the involvement of white adipose tissue in fetuin B-induced insulin resistance.