Transcriptional control of adipose tissue macrophages during high-fat diet-induced obesity.
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PROVIDER: PRJNA472395 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNA regulation of adipose tissue macrophages during high-fat diet-induced obesity.
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Project description:Macrophage-mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response. However, the role of Brd4 in obesity-associated inflammation and insulin resistance remains uncharacterized. Here, we demonstrated that myeloid-lineage specific Brd4 knockout (Brd4-CKO) mice were protected from high-fat-diet (HFD)-induced obesity with less fat accumulation, higher energy expenditure, and increased lipolysis in adipose tissue. Brd4-CKO mice also displayed reduced local and systemic inflammation with improved insulin sensitivity upon HFD. RNA-sequencing of adipose tissue macrophages (ATMs) from HFD-fed wide-type and Brd4-CKO mice revealed that expression of antilipolytic factor Gdf3 was significantly decreased in ATMs of Brd4-CKO mice. We also found that Brd4 bound to the promoter and enhancers of Gdf3 to facilitate PPARγ-dependent Gdf3 expression in macrophages. Furthermore, Brd4-mediated expression of Gdf3 acted as a paracrine signal targeting adipocytes to suppress the expression of lipases and the associated lipolysis in cultured cells and mice. Controlling the expression of Gdf3 in ATMs could be one of the mechanisms by which Brd4 modulates lipid metabolism and diet-induced obesity. This study suggests that Brd4 could be a potential therapeutic target for obesity and insulin resistance.
2021-03-24 | GSE169475 | GEO
Project description:DNA methylation-mediated regulation of adipose tissue macrophages during high-fat diet-induced obesity
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Project description:Obesity is a global health concern affecting over 650 million adults with a major contributor being an increased consumption of a high-fat diet. Maternal obesity often results in an increased risk of offspring developing obesity. In this study, we examined the effect of diet on visceral adipose in a pre-clinical model of generational diet-induced obesity that included maternal cohorts of C57BL/6 mice fed either a control diet (10% fat) or a high-fat diet (45% fat) and the resulting female offspring fed either diet. Using bottom-up proteomics on omental adipose tissue, differential protein expression was determined with the greatest difference resulting from the generational obese cohort. Differentially expressed proteins were involved in pathways related to cancer, inflammatory disease and immune response. Taken together, the results of this study provide molecular-level insight that will enable the development of more targeted, modifiable interventions that could be implemented pre-, during and post-pregnancy.
2024-10-17 | PXD042092 | Pride
Project description:Obesity is associated with an increased incidence of high grade prostate cancer (PC) and worse prognosis for PC patients. Recently, we showed in men that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures, was associated with high grade PC. Possibly, interventions that suppress periprostatic WAT inflammation will improve outcomes for men with PC. Prior to testing interventions we conducted this study to identify transcriptomic differences in periprostatic fat from lean and obese mice. We hypothesized that periprostatic fat from obese mice would have a proinflammatory signature in gene expression pattern. To test our hypothesis that obese mice would develop molecular signatures of inflammation in periprostatic fat, we fed mice low fat diet or high fat diet for 12 weeks and then harvested periprostatic fat at sacrifice. RNA was isolated and analyzed from 5 lean and 5 obese mice and analyzed by microarray.
2019-07-22 | GSE123355 | GEO
Project description:The effect of dietary calcium and dairy proteins on adipose tissue gene expression profile in diet induced obesity Experiment Overall Design: 9-week-old C57Bl/6J-mice were divided into two groups (n=10/group). The control diet was a standard high-fat diet (60% of energy) low in calcium (0.4%). The whey protein diet was a high-calcium (1.8%) high-fat diet with whey protein isolate. After the 21-week treatment, the adipose tissue transcript profiling (2 mice/group) was carried out using Affymetrix Mouse Genome 430 2.0 array.
2008-04-07 | E-GEOD-9280 | biostudies-arrayexpress
Project description:During obesity progression differential expression of microRNAs (miRs) play a role in effector (Teff) functions. A set of high fat diet adipose tissue derived immune cell miRs shows profound upregulation or downregulation in the expression profile as compared to normal diet.
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Project description:Background: Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of pro-inflammatory mediators, including TNFalpha and IL-6. Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages towards a more classical and pro-inflammatory phenotype. Here, we explore the effect of PPARγ-activation on obesity-induced inflammation in 129SV mice fed a high fat diet for 20 weeks. High fat feeding increased bodyweight gain, adipose tissue mass and liver triglycerides. Rosiglitazone treatment further increased adipose mass, reduced liver triglycerides and changed adipose tissue morphology towards smaller adipocytes. Surprisingly, rosiglitazone markedly increased the number of macrophages in adipose tissue, as shown by immunohistochemical analysis and quantification of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers for classically activated macrophages including IL-18 were down regulated whereas markers characteristic for alternatively activated macrophages (Arginase 1, IL-10) were up regulated by rosiglitazone. Importantly, conditioned media from rosiglitazone-treated alternatively activated macrophages neutralized the inhibitory effect of macrophages on 3T3-L1 adipocyte differentiation, suggesting that alternatively activated macrophages may be involved in mediating the effects of rosiglitazone on adipose tissue morphology and mass. Our results suggest that short term rosiglitazone treatment increases infiltration of alternatively activated macrophages in adipose tissue. The alternatively activated macrophages might play a role in PPARγ-dependent expansion and remodeling of adipose tissue. Keywords: metabolic state analysis Pure bred wild-type (129S1/SvImJ) male mice received a low fat diet or high fat diet for 21 weeks, providing 10 or 45% energy percent in the form of triglycerides (D12450B or D12451, Research Diets, New Brunswick, USA). The lard component in these diets was replaced by palm oil. In the last week of diet intervention, half of the mice receiving the HFD were switched to HFD supplemented with Rosiglitazone (0.01 % wt/wt). Animals were sacrificed in the fed state. Epididymal adipose tissue was excised and frozen in liquid nitrogen. Pooled RNA samples from 5 mice per experimental group were used for microarray analysis. Samples were hybridized on Affymetrix GeneChip Mouse Genome 430-2.0 plus arrays. Five microgram total RNA was labelled according to the Affymetrix One-cycle Target Labeling Assay, fragmented and hybridized according to Affymetrix's protocols.
2008-04-29 | E-GEOD-11295 | biostudies-arrayexpress
Project description:Effect of high fat diet feeding on adipose tissue macrophages
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Project description:Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from the development of inflammation and obesity under normal feeding conditions, and the progression to metabolic dysfunction under dietary stress. Genetic ablation of SIRT1 from adipose tissue leads to gene expression changes that highly overlap with changes induced by high fat diet in wild type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high fat diet induces the cleavage of SIRT1 in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction. Four replicates from four different biological conditions: 1) SIRT1 wild-type fed low fat diet, 2) SIRT1 wild-type fed high fat diet, 3) SIRT1 knock-out fed low fat diet, 4) SIRT1 knock-out fed high fat diet
2012-12-21 | E-GEOD-30247 | biostudies-arrayexpress