Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat.

ABSTRACT: Cold- and ?3-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-? 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-?(+) progenitor cells, as well as in human WAT-PDGFR-?(+) 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.

SUBMITTER: Seki T 

PROVIDER: S-EPMC4980448 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature