Male and female flow sorted adipose tissue macrophages and hematopoietic stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE181841 | GEO | 2022/03/07
REPOSITORIES: GEO
Similar Datasets
Project description:Adipose tissue stromal cells contribute to the regulation of adipose tissue in lean and obese states. Myeloid cells such as adipose tissue macrophages (ATMs) and dendritic cells (ATDCs) undergo both quantitative and qualitative changes with obesity. Due to similarity in markers the identify of adipose tissue dendritic cells and macrophages has been elusive. We have refined prior protocols to unambiguously discern ATM and ATDC in mice. We used microarrays to compare the profiles of ATMs and ATDC from gonadal adipose tissue from lean, obese, and formerly obese mice. We also isolated preadipocytes (PA) from lean and obese mice for comparison. Male C57Bl/6 mice were fed normal diet (ND) or high fat diet (HFD) for 16 weeks. Weight loss (WL) mice were switched from the HFD to ND for 8 weeks. RNA was purified from FACS sorted cell populations (live cells only) obtained from gonadal/epididymal adipose tissue depots. ATMs were defined as CD11c+ (CD45+CD64+ CD11c+) or CD11c- (CD45+CD64+ CD11c-) ATMs. ATDC were defined as CD64- CD11c+. PA were defined as CD31- CD45- Sca1+ PDGFRA+.
2016-09-01 | GSE85846 | GEO
Project description:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam cell–like cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization. 15 samples; 2 genotypes and 2 time points
2012-03-22 | E-GEOD-36669 | biostudies-arrayexpress
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:Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions. F4/80-positive ATMs were isolated from obese vs lean mice. High-fat feeding of wild-type mice and myeloid-specific Hif1α-/- mice was used to examine the role of hypoxia-inducible factor-1α (HIF-1α) in ATMs part of obese adipose tissue. In vitro, bone marrow-derived macrophages were co-cultured with adipose tissue explants to examine adipose tissue-induced changes in macrophage phenotypes. Transcriptome analysis, real-time flux measurements, ELISA and several other approaches were used to determine the metabolic signatures and inflammatory status of macrophages. In addition, various metabolic routes were inhibited to determine their relevance for cytokine production. Transcriptome analysis and extracellular flux measurements of mouse ATMs revealed unique metabolic rewiring in obesity characterised by both increased glycolysis and oxidative phosphorylation. Similar metabolic activation of CD14+ cells in obese individuals was associated with diabetes outcome. These changes were not observed in peritoneal macrophages from obese vs lean mice and did not resemble metabolic rewiring in M1-primed macrophages. Instead, metabolic activation of macrophages was dose-dependently induced by a set of adipose tissue-derived factors that could not be reduced to leptin or lactate. Using metabolic inhibitors, we identified various metabolic routes, including fatty acid oxidation, glycolysis and glutaminolysis, that contributed to cytokine release by ATMs in lean adipose tissue. Glycolysis appeared to be the main contributor to the proinflammatory trait of macrophages in obese adipose tissue. HIF-1α, a key regulator of glycolysis, nonetheless appeared to play no critical role in proinflammatory activation of ATMs during early stages of obesity. Our results reveal unique metabolic activation of ATMs in obesity that promotes inflammatory cytokine release. Further understanding of metabolic programming in ATMs will most likely lead to novel therapeutic targets to curtail inflammatory responses in obesity.
2018-02-02 | GSE84000 | GEO
Project description:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam cell–like cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
2012-03-22 | GSE36669 | GEO
Project description:Glycyrrhetinic acid (GA) and its derivative, magnesium isoglycyrrhizinate, exhibit promising anti-obesity effects through mechanisms that are not fully understood. Here, we showed that GA mitigated white adipose tissue remodeling and diet-induced obesity by enhancing lipid catabolism. GA indirectly promoted adipocyte lipolysis and thermogenesis by modulating catecholamine pathways, facilitated by increased intra-fat sympathetic innervation and reduced protein expression of monoamine oxidase A (MAOA), which degrades norepinephrine. In suit visualization of MAOA identified adipose tissue macrophages (ATMs) as key mediators of intra-fat catecholamine degradation. RNA sequencing of sorted ATMs revealed that GA reduced pro-inflammatory shifts and altered macrophage polarity, preventing activation of the Toll-like receptor 4 (TLR4) signaling pathway, as supported by molecular docking analysis and binding assays. Moreover, the anti-obesity effects of GA were absent in TLR4-deletive mice, which exhibited decreased MAOA protein levels and sensitivity to FUNDC1-mediated mitophagy in ATMs. These findings suggest that GA targets macrophage-sympathetic neuron crosstalk, offering a promising therapeutic approach for obesity by preserving NE availability and promoting lipid catabolism.
2024-10-01 | GSE273958 | GEO
Project description:To determine how the miR-23-27-24 miRNA clusters regulate adipose tissue macrophage (ATM) programming in obesity, we placed control mice and mice containing a myeloid-specific deletion of the clusters on high-fat diet for 20weeks. Following dietary intervention, we performed bulk RNA-seq on F4/80 bead-selected ATMs from obese adipose tissue of control and knockout mice.
2023-06-30 | GSE222351 | GEO
Project description:We report sustained changes in the chromatin accessibility landscape of adipose tissue macrophages (ATMs) from high fat diet (HFD)-fed mice persist long after return to regular diet (RD). We compared the data of ATAC-seq performed on nuclei extracted from FACS-sorted ATMs isolated from HFD, RD-RD and HFD-RD-fed mice. Inter-group comparisons revealed the highest diversity and hence the greatest number of differentially accessible regions (DARs) to occur between ATMs from RD-RD and HFD-RD-fed mice, and considerably fewer DARs were identified between ATMs from HFD-RD vs HFD-fed mice. Association of DARs with the nearest gene and gene ontology (GO) enrichment analysis revealed considerable pathway enrichment, especially pathways coding for angiogenesis and inflammatory response, in HFD-RD group when compared to RD-RD group. The results altogether indicated that most changes in chromatin landscape induced by HFD-feeding are maintained as open chromatin positions for a long time, suggesting that HFD-feeding leads to long-term reprograming of ATMs and renders them prone to pro-angiogenic and pro-inflammatory responses.
2024-01-25 | GSE175614 | 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:In mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice. We used expression microarrays to generate transcription profiles of perigonadal ATMs from lean (C57BL/6J Lep +/+) and obese (C57BL/6J Lep ob/ob) mice. Profiling purified FBs and FBCs, we identified 521 transcripts whose expression was differentially (nominal p-value < 0.01) expressed between FBs from lean and obese mice and 1509 genes whose expression was differentially (nominal p-value <0.01) expressed between FBC from lean and obese mice RNA was isolated from sorted FBC (F4/80+, CD11b+, CD11c+) cells and FB ( F4/80+, CD11b+, CD11c-) cells and using RNeasy micro-kits (Qiagen), using a PicoPure RNA isolation kit then amplified two-rounds. Labeled cRNA Mouse Genome 430 2.0 arrays (purified FB and FBC adipose tissue macrophages. There was a total of sixteen samples. FB and FBC populations were isolated from 4 lean and 4 obese mice.
2013-12-18 | E-GEOD-53403 | biostudies-arrayexpress