Fetuin B Is Related to Cytokine/Chemokine and Insulin Signaling in Adipose Tissue and Plasma in Humans.

Context: 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.

Objective: 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 center (model 1); model 1 + BMI (model 2); and model 2 + insulin sensitivity (Matsuda index) (model 3).

Results: Plasma fetuin B was associated with more than 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 more than 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.