Lucia Berti1,2,3, Sonja Hartwig3,4, Martin Irmler2,3, Bernhard Rädle2,3, Dorothea Siegel-Axel1,3,5, Johannes Beckers2,3,6, Stefan Lehr3,4, Hadi Al-Hasani3,4, Hans-Ulrich Häring1,3,5, Martin Hrabě de Angelis2,3,6, Harald Staiger1,3,5. 1. a Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen , Tübingen , Germany. 2. b Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Experimental Genetics , Neuherberg , Germany. 3. c German Centre for Diabetes Research (DZD) , Neuherberg , Germany. 4. d Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf , Düsseldorf , Germany. 5. e Department of Internal Medicine , Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen , Tübingen , Germany , and. 6. f Chair for Experimental Genetics, Technical University Munich , Neuherberg , Germany.
Abstract
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.
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.