RNA-seq analysis of high fat diet-induced changes in macrophage transcriptome
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126887 | GEO | 2020/01/30
REPOSITORIES: GEO
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Project description:We studied macrophage gene expression from mice fed chow diet (C) or 60% high fat diet (HF), that phagocytized C-RBC, HFD-RBC, or no RBC. Macrophages from mice on HF diet were activated toward a pro-inflammatory phenotype. In macrophages isolated from CD mice, RBC phagocytosis yielded a gene expression pattern similar to HF macrophages. Incubation of HF-RBC with macrophages resulted in a significantly more pronounced upregulation of pro-inflammatory chemokines as compared to C-RBC. Peritoneal macrophages were obtained from C57BL/6 mice fed either C or HF diet. Phagocytosis was performed in vitro with C-RBC or HF-RBC; macrophages not exposed to RBC served as a control. Affymetrix Mouse Gene 1.0 ST microarray chips were used to assess the gene expression profile.
2013-08-28 | E-GEOD-50240 | biostudies-arrayexpress
Project description:Background: Atherosclerosis leads high mortality, highlighting an urgent need for new therapeutic strategies. Protein kinases orchestrate multiple cellular events in atherosclerosis and may provide new therapeutic targets for atherosclerosis. Here, we identified a protein kinase, WEE1 G2 checkpoint kinase (WEE1), promoting inflammatory response in atherosclerosis. Methods: The ApoE-/- mice without macrophage-specific WEE1 deletion (ApoE-/-WEE1f/f) and ApoE-/- mice with macrophage-specific WEE1 deletion (ApoE-/-WEE1MCKO) were generated using bone marrow transplantation. These mice and WEE1 inhibitor MK1775 were used in a high-fat diet (HFD)-induced atherosclerotic model. Human atherosclerotic tissues, mouse primary peritoneal macrophages (MPMs), 293T cells, and recombinant proteins were utilized to investigate the pathogenic role and underlying mechanisms of WEE1. Results: We identified up-regulated p-WEE1 in macrophages in atherosclerotic lesions of HFD-fed ApoE-/- mice. Transcriptome sequencing analysis indicated that WEE1 promotes oxLDL-induced inflammation in macrophages. We then demonstrated that macrophage-specific deletion or pharmacological inhibition of WEE1 attenuates atherosclerosis by reducing inflammation both in vivo and in vitro. The overexpression of wild-type WEE1 or activating-mutant WEE1, but not inactivating-mutant WEE1, exacerbates inflammation in macrophages. Mechanistically, transcriptome sequencing analysis and co-immunoprecipitation followed by quantitative proteomics analysis identified p65 as a binding protein of WEE1. We confirmed that WEE1 directly interacts with the RHD domain of p65 via kinase domain and phosphorylates p65 at S536, thereby facilitating subsequent NF-κB activation and inflammatory response in macrophages. Conclusions: Our findings demonstrated that macrophage WEE1 promotes inflammatory atherosclerosis by directly binding to p65 and phosphorylate it at S536. This study provides WEE1 as a new p65 regulator in inflammation and a potential therapeutic target for atherosclerosis.
2024-03-25 | PXD050932 | Pride
Project description:Obesity, characterized by augmented inflammation and tumorigenesis, is linked to genetic predispositions, such as FOXO3 polymorphisms. As obesity is associated with aberrant macrophages infiltrating different tissue including the colon, we aimed to identify FOXO3-dependent transcriptomic changes in macrophages that drive obesity-mediated colonic inflammation and tumorigenesis. We found that in mouse colons, high-fat-diet-(HFD)-obesity led to diminished FOXO3 levels and increased macrophages. Transcriptomic analysis of mouse peritoneal FOXO3-deficient macrophages showed significant differentially expressed genes (DEGs; FDR<0.05) similar to HFD-obese colon. These DEGs related pathways, linked to mouse colonic inflammation and tumorigenesis, were similar to those in inflammatory bowel disease (IBD) and human colon cancer. Additionally, we identified a specific transcriptional signature for the macrophage-FOXO3 axis (MAC-FOXO382), which separated the transcriptome of affected tissue from control in both IBD (p=5.2E-08) and colon cancer (p=1.9E-11), revealing its significance in human colonic pathobiologies. Further, we identified (heatmap) and validated (qPCR) DEGs specific to FOXO3-deficient macrophages with established roles both in IBD and colon cancer (IL-1B, CXCR2, S100A8, S100A9, and TREM1) and those with unexamined roles in these colonic pathobiologies (STRA6, SERPINH1, LAMB1, NFE2L3, OLR1, DNAJC28 and VSIG10). These findings establish an important understanding of how HFD-obesity and related metabolites promote colonic pathobiologies.
2022-03-14 | GSE198058 | GEO
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:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course In this study, C57BL/6J mice were fed a high fat (HF) diet for 8 weeks to induce obesity and insulin resistance. Plasma levels of the adipokines leptin and adiponectin were measured. To investigate how these metabolic disturbances will influence the skeletal muscle transcriptome we performed whole-genome microarray analysis. Functional implications were assessed by analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways.
2010-08-10 | E-GEOD-17576 | biostudies-arrayexpress
Project description:The arrays were used to explore how parents’ obesity status influence their offspring’s weight. We randomly assigned three-week-old mice to two groups, one group receiving a high-fat diet (HFD), the other group receiving a control diet (chow). Adult females of both groups were mated to males fed with HFD or CD. F1 transcriptome assay data were created from four tissues (liver, epigonal visceral, inguinal subcutaneous, and interscapular brown adipose tissue) of male offspring in relation to their parents’ obesity status.
2023-11-30 | E-MTAB-13493 | biostudies-arrayexpress
Project description:Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes. Gene arrays were performed on epidydimal white adipose tissue samples from wild type and human IL37-overexpressing transgenic mice fed a high fat diet for 16 weeks.
2015-05-18 | E-GEOD-58952 | biostudies-arrayexpress
Project description:Time-course analysis of adipocyte gene expression profiles response to high fat diet. The hypothesis tested in the present study was that in diet-induced obesity, early activation of TLR-mediated inflammatory signaling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of a diet-induced obesity. Total RNA obtained from isolated epididymal and mesenteric adipose tissue of C57BL/6J mice fed normal diet or high fat diet for 2, 4, 8, 20 and 24weeks
2014-03-01 | E-GEOD-39549 | biostudies-arrayexpress
Project description:Obesity is tightly associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms of obesity-induced fatty liver remain largely unknown.In order to identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, we performed a clustering analysis of Affymetrix arrays,which revealed that a number of mRNAs were dys-regulated in the livers of mice fed a high-fat diet (HFD), compared with mice fed a normal chow diet (ND). To identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, male C57BL/6 mice aged 8 weeks were fed a normal diet (ND) or high-fat-diet (HFD) containing 60 Kcal% of fat for 12 weeks. Then mice were sacrificed and total RNAs were isoloated from hepatic tissues. Affymetrix array hybridisation and scanning were performed using Mouse Genome 430 2.0 chips.Total RNA samples obtained from six mice per group (ND and HFD) and pooled by each of the two were used for microarray analysis.
2014-05-09 | E-GEOD-57425 | biostudies-arrayexpress
Project description:We explored early changes in gene expression in the livers and lungs of the HFD-fed, metastasizing mammary tumor-bearing and obesity-resistant mice mice. These alterations may have led to favorable conditions for both the formation of pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as infiltration and proliferation of metastatic tumor cells. Total RNA was isolated from hepatic and pulmonary tissues of high fat diet fed-4T1 cell-injected mice or high fat diet fed-sham mice. Gene expressions were compared to control diet fed-same conditional mice.
2012-03-05 | E-GEOD-36211 | biostudies-arrayexpress