Mus musculus
Ontology highlight
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:Adipocyte hypertrophy during obesity triggers chronic inflammation, leading to metabolic disorders. However, the role of adipocyte-specific inflammatory signalling in metabolic syndrome remains unclear. The linear ubiquitin chain assembly complex, LUBAC, is an E3-ligase that generates non-degradative linear ubiquitination (Lin-Ub). LUBAC regulates NF-κB/MAPK-driven inflammation and prevents cell death triggered by immune receptors like TNF-receptor-1. Here we show that mice lacking HOIP, LUBAC’s catalytic subunit, in adipocytes (HoipA-KO) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Mechanistically, loss of HOIP attenuates TNF-induced NF-κB activation and promotes cell death in human adipocytes. Inhibiting caspase-8-mediated cell death is sufficient to prevent lipodystrophy and MASLD in HoipA-KO obese mice. Importantly, HOIP expression in adipose tissue positively correlates with metabolic fitness in obese individuals. Overall, our findings reveal a critical role for Lin-Ub in protecting against obesity-related metabolic syndrome by mitigating cell death-driven adipose tissue inflammation
2025-09-03 | GSE293034 | GEO
Project description:Adipocyte hypertrophy during obesity triggers chronic inflammation, leading to metabolic disorders. However, the role of adipocyte-specific inflammatory signalling in metabolic syndrome remains unclear. The linear ubiquitin chain assembly complex, LUBAC, is an E3-ligase that generates non-degradative linear ubiquitination (Lin-Ub). LUBAC regulates NF-κB/MAPK-driven inflammation and prevents cell death triggered by immune receptors like TNF-receptor-1. Here we show that mice lacking HOIP, LUBAC’s catalytic subunit, in adipocytes (HoipA-KO) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Mechanistically, loss of HOIP attenuates TNF-induced NF-κB activation and promotes cell death in human adipocytes. Inhibiting caspase-8-mediated cell death is sufficient to prevent lipodystrophy and MASLD in HoipA-KO obese mice. Importantly, HOIP expression in adipose tissue positively correlates with metabolic fitness in obese individuals. Overall, our findings reveal a fundamental developmental role for Lin-Ub in adipocytes by mitigating cell death-driven adipose tissue inflammation and protecting against obesity-related metabolic
2025-08-22 | GSE298555 | 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:As obesity progresses, dynamic tissue remodeling of adipose tissue occurs over time, i.e., adipocyte hypertrophy, chronic inflammation, and interstitial fibrosis. Some obese individuals exhibit healthy adipose tissue expansion, characterized by modest inflammation and fibrosis despite adipocyte hypertrophy, resulting in “Metabolically Healthy Obesity (MHO)”. Our research has revealed that MHO can be induced by temporary weight loss during the development of obesity.
2025-07-23 | GSE286421 | GEO
Project description:As obesity progresses, dynamic tissue remodeling of adipose tissue occurs over time, i.e., adipocyte hypertrophy, chronic inflammation, and interstitial fibrosis. Some obese individuals exhibit healthy adipose tissue expansion, characterized by modest inflammation and fibrosis despite adipocyte hypertrophy, resulting in “Metabolically Healthy Obesity (MHO)”. Our research has revealed that MHO can be induced by temporary weight loss during the development of obesity.
2025-07-23 | GSE286420 | GEO