Mus musculus
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ABSTRACT:
PROVIDER: PRJNA262524 | ENA |
REPOSITORIES: ENA
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Project description:Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases are essential regulators of inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. In this study, we found that the ubiquitin ligase Siah2 is a central factor in obesity-related adipose tissue inflammation. When challenged with chronic excess energy intake, Siah2-null mice become obese with enlarged adipocytes, but do not develop obesity-induced insulin resistance. Proinflammatory gene expression is substantially reduced in the Siah2-null epididymal adipose tissue of the obese Siah2KO mice.
2015-09-29 | GSE61839 | GEO
Project description:Analysis of gene expression altered upon knockdown of Siah2 in prosate cancer cells. The objective is to elucidate which signaling pathways or transcription factors are regulated by the E3 ubiquitin ligase Siah2 in human prostate cancer cells. CWR22Rv1 cells were in fected with pLKO.1 control or Siah2 shRNA, and selected with 1ug/ml of puromycin to get stable transfectants. Total RNA was extracted for micorarray analysis to compare the diffentially expressed genes between pLKO.1 control and Siah2 knockdown cells.
2013-03-19 | E-GEOD-38851 | biostudies-arrayexpress
Project description:Analysis of gene expression altered upon knockdown of Siah2 in prosate cancer cells. The objective is to elucidate which signaling pathways or transcription factors are regulated by the E3 ubiquitin ligase Siah2 in human prostate cancer cells.
2013-03-19 | GSE38851 | GEO
Project description:Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis to cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA (mtDNA) content and mitochondrial function are significantly increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion robustly elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated Nqo1. Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mtDNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.
2022-09-29 | GSE207496 | GEO
Project description:M1 macrophages induce protective immunity against infection, but also contribute to metabolic and inflammatory diseases. Here we show that he E3 ubiquitin ligase, MDM2, promotes the glycolytic and inflammatory activities of M1 macrophage by increasing the production of IL-1β, MCP-1 and nitric oxide (NO). Mechanistically, MDM2 triggers the ubiquitination and degradation of E3 ligase, SPSB2, to stabilize iNOS and increases production of NO, which s-nitrosylates and activates HIF-1α for triggering the glycolytic and pro-inflammatory programs in M1 macrophages. Myeloid-specific haplo-deletion of MDM2 in mice not only blunts LPS-induced endotoxemia and NO production, but also alleviates obesity-induced adipose tissue-resident macrophage inflammation. By contrast, MDM2 haplodeletion induces higher mortality, tissue damage and bacterial burden, and also suppresses M1 macrophage response, in the cecal ligation and puncture-induced sepsis mouse model. Our findings thus identify MDM2 as an activator of glycolytic and inflammatory responses in M1 macrophages by connecting the iNOS-NO and HIF-1α pathways.
2024-09-16 | GSE276736 | GEO
Project description:The androgen receptor (AR) plays a central role in the development of castration resistant prostate cancer (CRPC). Here, we demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound, transcriptionally inactive AR for ubiquitination dependent degradation, thereby promoting the expression of ~13% of AR target genes. The Siah2 binding sites located within the AR ligand-binding domain are mutated in PCa, resulting in attenuation of Siah2-mediated regulation. Siah2 is required for growth of PCa cells under androgen-deprivation conditions in vitro and in vivo. Significantly, inhibition of Siah2 promotes PCa regression upon castration and Siah2 expression is markedly increased in human CRPCs. Collectively our findings identify a key role for Siah2 in CRPC through the selective regulation of AR transcriptional activity.
2013-02-15 | GSE44319 | GEO
Project description:Obesity leads to a state of chronic low-grade inflammation that features accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid droplet accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages could be rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.
2019-12-19 | GSE142294 | GEO
Project description:Obesity leads to a state of chronic low-grade inflammation that features accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid droplet accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages could be rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.
2019-12-19 | GSE142295 | GEO
Project description:To assess changes in expression level of various chemokines and their receptors on diet-induced obesity, we analysed gene expression in adipose tissue of C56BL/6J mice fed a high-fat (HF) diet or normal chow diet for 8 weeks. HF diet-induced obese (DIO) mice showed adipose tissue inflammation and insulin resistance. Comprehensive gene expression analysis showed that MCP-1–CCR2 and CCL5–CCR5 signalling in epididymal white adipose tissue (eWAT) were enhanced during the development of obesity. Surprisingly, the gene expression of Cx3cl1 was decreased in the eWAT of DIO mice compared with lean mice. While Cx3cr1 expression showed no significant difference between DIO and lean mice. Decreased CX3CL1-CX3CR1 signalling in adipose tissue may also be involved in the development of obesity-induced adipose tissue inflammation and insulin resistance.
2021-04-01 | GSE167311 | GEO
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