Diet-regulated production of PDGFcc by macrophages controls energy storage.
Nehemiah CoxLucile CrozetInge R HoltmanPierre-Louis LoyherTomi LazarovJessica B WhiteElvira MassE Richard StanleyOlivier ElementoChristopher K GlassFrederic GeissmannPublished in: Science (New York, N.Y.) (2021)
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.
Keyphrases
- adipose tissue
- vascular endothelial growth factor
- growth factor
- fatty acid
- insulin resistance
- physical activity
- high fat diet
- endothelial cells
- weight loss
- transcription factor
- high fat diet induced
- copy number
- metabolic syndrome
- genome wide
- dna methylation
- cell cycle arrest
- type diabetes
- big data
- smooth muscle
- signaling pathway
- cell proliferation
- endoplasmic reticulum stress