| First Author | Shan B | Year | 2020 |
| Journal | Nat Metab | Volume | 2 |
| Issue | 11 | Pages | 1332-1349 |
| PubMed ID | 33139957 | Mgi Jnum | J:350396 |
| Mgi Id | MGI:6727671 | Doi | 10.1038/s42255-020-00301-7 |
| Citation | Shan B, et al. (2020) Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity. Nat Metab 2(11):1332-1349 |
| abstractText | 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 (PDGFRbeta(+)) 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-kappaB. ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NF-kappaB by inducing a p300-to-NuRD coregulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRbeta(+) cells suppresses inflammatory signalling in FIPs and attenuates metabolic inflammation of visceral WAT in obesity. Inducible inactivation of Zfp423 in PDGFRbeta(+) 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-kappaB signalling. |
