Diet-regulated production of PDGFcc by macrophages controls energy storage

被引：83

作者：

Cox, Nehemiah ^{[1
]}

Crozet, Lucile ^{[1
,2
]}

Holtman, Inge R. ^{[3
]}

Loyher, Pierre-Louis ^{[1
]}

Lazarov, Tomi ^{[1
,2
]}

White, Jessica B. ^{[2
]}

Mass, Elvira ^{[1
,4
]}

Stanley, E. Richard ^{[5
]}

Elemento, Olivier ^{[6
,7
]}

Glass, Christopher K. ^{[3
]}

Geissmann, Frederic ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Immunol Program, New York, NY 10065 USA

[2] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA

[3] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA

[4] Univ Bonn, LIMES Inst, Dev Biol Immune Syst, D-53115 Bonn, Germany

[5] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA

[6] Weill Cornell Med, Dept Physiol & Biophys, Inst Computat Biomed, New York, NY 10065 USA

[7] Weill Cornell Med, Caryl & Israel Englander Inst Precis Med, New York, NY 10065 USA

来源：

SCIENCE | 2021年 / 373卷 / 6550期

关键词：

ADIPOSE-TISSUE MACROPHAGES; CHEMOKINE RECEPTOR 2; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; MYELOID CELLS; GLUCOSE-HOMEOSTASIS; GENE-EXPRESSION; FAT-BODY; RNA-SEQ; OBESITY;

D O I：

10.1126/science.abe9383

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：37

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