TY - JOUR
T1 - Diet-regulated production of PDGFcc by macrophages controls energy storage
AU - Cox, Nehemiah
AU - Crozet, Lucile
AU - Holtman, Inge R.
AU - Loyher, Pierre Louis
AU - Lazarov, Tomi
AU - White, Jessica B.
AU - Mass, Elvira
AU - Stanley, E. Richard
AU - Elemento, Olivier
AU - Glass, Christopher K.
AU - Geissmann, Frederic
N1 - Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.
PY - 2021/7/2
Y1 - 2021/7/2
N2 - 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.
AB - 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.
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U2 - 10.1126/science.abe9383
DO - 10.1126/science.abe9383
M3 - Article
C2 - 34210853
AN - SCOPUS:85109117460
SN - 0036-8075
VL - 373
JO - Science
JF - Science
IS - 6550
M1 - eabe9383
ER -