Diet-regulated production of PDGFcc by macrophages controls energy storage.

TitleDiet-regulated production of PDGFcc by macrophages controls energy storage.
Publication TypeJournal Article
Year of Publication2021
AuthorsCox N, Crozet L, Holtman IR, Loyher P-L, Lazarov T, White JB, Mass E, E Stanley R, Elemento O, Glass CK, Geissmann F
Date Published2021 07 02
KeywordsAdipocytes, Adipose Tissue, Brown, Animals, Diet, High-Fat, Drosophila melanogaster, Drosophila Proteins, Energy Metabolism, Female, Hemocytes, Liver, Lymphokines, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Obesity, Platelet-Derived Growth Factor, Receptors, CCR2, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Thermogenesis, Vascular Endothelial Growth Factor A

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 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.

Alternate JournalScience
PubMed ID34210853
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 AI130345 / AI / NIAID NIH HHS / United States
R01 HL138090 / HL / NHLBI NIH HHS / United States
F32 CA225036 / CA / NCI NIH HHS / United States