Impact of fibroblast growth factor 21 on the secretome of human perivascular preadipocytes and adipocytes: a targeted proteomics approach

Context: Perivascular adipose tissue (PVAT) is suggested to impact on vascular cells via humoral factors, possibly contributing to endothelial dysfunction and atherosclerosis. Objective: To address whether the hepatokine fibroblast growth factor (FGF) 21 affects the PVAT secretome. Methods: Human perivascular (pre)adipocytes were subjected to targeted proteomics and whole-genome gene expression analysis. Results: Preadipocytes, as compared to adipocytes, secreted higher amounts of inflammatory cytokines and chemokines. Adipocytes released higher amounts of adipokines [e.g. adipisin, visfatin, dipeptidyl peptidase 4 (DPP4), leptin; p < 0.05, all]. In preadipocytes, omentin 1 release was 1.28-fold increased by FGF-21 (p < 0.05). In adipocytes, FGF-21 reduced chemerin release by 5% and enhanced DPP4 release by 1.15-fold (p < 0.05, both). FGF-21 altered the expression of four secretory genes in preadipocytes and of 18 in adipocytes (p < 0.01, all). Conclusion: The hepatokine FGF-21 exerts secretome-modulating effects in human perivascular (pre)adipocytes establishing a new liver-PVAT-blood vessel axis that possibly contributes to vascular inflammation and atherosclerosis.