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

ABSTRACT: 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

SUBMITTER: Shan B 

PROVIDER: S-EPMC7669663 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature