title: Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat.
abstract: Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose tissues. Here we show that endothelial production of PDGF-CC during white adipose tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion of endothelial VEGFR2, knockout of the Pdgf-c gene or pharmacological blockade of PDGFR-α impair the WAT-beige transition. We further show that PDGF-CC stimulation upregulates UCP1 expression and acquisition of a beige phenotype in differentiated mouse WAT-PDGFR-α(+) progenitor cells, as well as in human WAT-PDGFR-α(+) adipocytes, supporting the physiological relevance of our findings. Our data reveal a paracrine mechanism by which angiogenic endothelial cells modulate adipocyte metabolism, which may provide new targets for the treatment of obesity and related metabolic diseases.
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Takahiro
authors: T
authors: Seki
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Kayoko
authors: K
authors: Hosaka
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Sharon
authors: S
authors: Lim
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Carina
authors: C
authors: Fischer
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Jennifer
authors: J
authors: Honek
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Yunlong
authors: Y
authors: Yang
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Patrik
authors: P
authors: Andersson
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Masaki
authors: M
authors: Nakamura
authors: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm 182 88, Sweden.
authors: Erik
authors: E
authors: Näslund
authors: Department of Molecular Medicine, A.I. Virtanen Institute, Molecular Sciences University of Eastern Finland, Kuopio 70211, Finland.
authors: Seppo
authors: S
authors: Ylä-Herttuala
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Meili
authors: M
authors: Sun
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Hideki
authors: H
authors: Iwamoto
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors: Xuri
authors: X
authors: Li
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors: Yizhi
authors: Y
authors: Liu
authors: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors: Nilesh J
authors: NJ
authors: Samani
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.|Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors: Yihai
authors: Y
authors: Cao
mesh_terms: D000069796:Adipose Tissue, Beige / Q000098:blood supply* / Q000502:physiology*; D000818:Animals; D059305:Diet, High-Fat; D004149:Dioxoles / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D004149:Dioxoles; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011941:Receptors, Adrenergic; D000071256:Uncoupling Protein 1; D042461:Vascular Endothelial Growth Factor A; C411423:platelet-derived growth factor C; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2