Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity.

Journal Article (Journal Article)

Chronic low-grade white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a subpopulation of mouse WAT perivascular (PDGFRβ+) cells, termed fibro-inflammatory progenitors (FIPs), activate proinflammatory signalling cascades shortly after the onset of high-fat diet feeding and regulate proinflammatory macrophage accumulation in WAT in a TLR4-dependent manner. FIPs activation in obesity is mediated by the downregulation of zinc-finger protein 423 (ZFP423), identified here as a transcriptional corepressor of NF-κB. ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NF-κB by inducing a p300-to-NuRD coregulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRβ+ cells suppresses inflammatory signalling in FIPs and attenuates metabolic inflammation of visceral WAT in obesity. Inducible inactivation of Zfp423 in PDGFRβ+ cells increases FIP activity, exacerbates adipose macrophage accrual and promotes WAT dysfunction. These studies implicate perivascular mesenchymal cells as important regulators of chronic adipose-tissue inflammation in obesity and identify ZFP423 as a transcriptional break on NF-κB signalling.

Full Text

Duke Authors

Cited Authors

  • Shan, B; Shao, M; Zhang, Q; Hepler, C; Paschoal, VA; Barnes, SD; Vishvanath, L; An, YA; Jia, L; Malladi, VS; Strand, DW; Gupta, OT; Elmquist, JK; Oh, D; Gupta, RK

Published Date

  • November 2020

Published In

Volume / Issue

  • 2 / 11

Start / End Page

  • 1332 - 1349

PubMed ID

  • 33139957

Pubmed Central ID

  • PMC7669663

Electronic International Standard Serial Number (EISSN)

  • 2522-5812

Digital Object Identifier (DOI)

  • 10.1038/s42255-020-00301-7


  • eng

Conference Location

  • Germany