Project description:Committed perivascular preadipocytes were genetically labelled in transgenic mice expressing GFP under the control of the locus (BAC) for Zfp423, a gene controlling preadipocyte determination. The overall goal was to identify genes differentially expressed between perivascular (PDGFRbeta+) GFP+ cells and perivascualar (PDGFRbeta+) GFP- cells from mouse epididymal adipose tissue.
Project description:Committed preadipocyte fibroblasts were genetically labelled in transgenic mice by expressing GFP under the control of the locus for Zfp423, a gene controlling preadipocyte determination. These mice are herein referred to as Zfp423-GFP mice. The overall goal was to identify genes differentially expressed between adipogenic GFP+ firboblasts and non-adipogenic GFP- fibroblasts from either inguinal or epididymal fat stromal vascular cultures obtained from Zfp423-GFP mice. Adipose stromal vascular cultures were obtained from inguinal or epididymal fat of 6-8 week-old male Zfp423-GFP mice. GFP+ and GFP- fibroblasts were sorted from fat stromal vascular cultures and then returned to culture. Subconfluent cultures of GFP+ and GFP- cells were compared in triplicate for Affymetrix analysis.
Project description:Chronic low-grade visceral white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a subpopulation of adipose tissue perivascular (PDGFRb+) cells, termed “fibro-inflammatory progenitors” (FIPs), activate pro-inflammatory signaling cascades shortly after the onset of high-fat diet feeding of mice and regulate pro-inflammatory macrophage accumulation in WAT in a TLR4-dependent manner. FIPs activation in obesity is mediated by the downregulation of ZFP423, identified here as a transcriptional co-regulator of NFkB. Biochemical analysis of ZFP423-protein complexes and ChIP-seq analysis reveal that ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NFkB by inducing a p300 to NuRD co-regulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRb+ cells suppresses inflammatory signaling in FIPs and attenuates metabolic inflammation of visceral WAT in obesity. Inducible inactivation of Zfp423 in PDGFRb+ 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 NFkB signaling.
Project description:Chronic low-grade visceral white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a specific subpopulation of adipose tissue perivascular (PDGFRb+) stromal cells, termed “fibro-inflammatory progenitors” (FIPs), activate pro-inflammatory signaling cascades shortly after the onset of high-fat diet feeding of mice and control the accumulation of pro-inflammatory macrophages in WAT. The activation of FIPs is mediated by the downregulation of ZFP423, identified here as a transcriptional co-regulator of NFkB. Biochemical analysis of ZFP423-protein complexes and ChIP-seq analysis reveal that ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NFkB by inducing a co-regulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRb+ cells suppresses inflammatory signaling in FIPs and attenuates macrophage accumulation within visceral WAT of obese mice. Conversely, inducible inactivation of Zfp423 in PDGFRb+ cells increases FIP activity, exacerbates adipose macrophage accrual, and promotes WAT dysfunction in obese mice. These studies implicate mural cells as sentinels and gatekeepers of adipose tissue inflammation in obesity.
Project description:Committed preadipocyte fibroblasts were genetically labelled in transgenic mice by expressing GFP under the control of the locus for Zfp423, a gene controlling preadipocyte determination. These mice are herein referred to as Zfp423-GFP mice. The overall goal was to identify genes differentially expressed between adipogenic GFP+ firboblasts and non-adipogenic GFP- fibroblasts from either inguinal or epididymal fat stromal vascular cultures obtained from Zfp423-GFP mice.
Project description:In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. To investigate molecular mechanisms underlying depot-specific metabolic roles, we report the transcriptomes of adipocytes and SVCs derived from NCD-fed mouse epididymal adipose tissue (EAT) or inguinal adipose tissues (IAT).
Project description:Identify genes in the epididymal adipose tissue whose expression is under genetic regulation in the hybrid mouse diversity panel. The hybrid mouse diversity panel is comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness. GWAS for expression of epididymal adipose tissue in inbred strains
Project description:Label-free LC-MS/MS was used to characterise and quantify the secretory profiles of murine perivascular adipose tissue, canonical white adipose tissue, and brown adipose tissue.
2022-11-15 | PXD031271 | Pride
Project description:Bulk RNA-seq of mouse epididymal adipose tissue