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

Nat Commun. 2016 Aug 5;7:12152. doi: 10.1038/ncomms12152.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Beige / blood supply*
  • Adipose Tissue, Beige / physiology*
  • Animals
  • Diet, High-Fat
  • Dioxoles / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Female
  • Gene Deletion
  • Humans
  • Intra-Abdominal Fat / metabolism
  • Lymphokines / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Neovascularization, Physiologic* / drug effects
  • Phenotype
  • Platelet-Derived Growth Factor / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptors, Adrenergic / metabolism
  • Thermogenesis* / drug effects
  • Uncoupling Protein 1 / metabolism
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Dioxoles
  • Lymphokines
  • Platelet-Derived Growth Factor
  • Receptors, Adrenergic
  • Uncoupling Protein 1
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor C
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
  • Receptor, Platelet-Derived Growth Factor alpha
  • Vascular Endothelial Growth Factor Receptor-2