Diet-regulated production of PDGFcc by macrophages controls energy storage

Science. 2021 Jul 2;373(6550):eabe9383. doi: 10.1126/science.abe9383.


The mechanisms by which macrophages regulate energy storage remain poorly understood. We identify in a genetic screen a platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF)-family ortholog, Pvf3, that is produced by macrophages and is required for lipid storage in fat-body cells of Drosophila larvae. Genetic and pharmacological experiments indicate that the mouse Pvf3 ortholog PDGFcc, produced by adipose tissue-resident macrophages, controls lipid storage in adipocytes in a leptin receptor- and C-C chemokine receptor type 2-independent manner. PDGFcc production is regulated by diet and acts in a paracrine manner to control lipid storage in adipose tissues of newborn and adult mice. At the organismal level upon PDGFcc blockade, excess lipids are redirected toward thermogenesis in brown fat. These data identify a macrophage-dependent mechanism, conducive to the design of pharmacological interventions, that controls energy storage in metazoans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / immunology*
  • Adipose Tissue, Brown / immunology
  • Animals
  • Diet, High-Fat*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Energy Metabolism*
  • Female
  • Hemocytes / immunology
  • Liver / immunology
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / immunology*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism*
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Thermogenesis*
  • Vascular Endothelial Growth Factor A / metabolism


  • Ccr2 protein, mouse
  • Csf1r protein, mouse
  • Drosophila Proteins
  • Lymphokines
  • PVF3 protein, Drosophila
  • Platelet-Derived Growth Factor
  • Receptors, CCR2
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor C