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Sex-dependent effects of Siah2 on brown adipose tissue whitening and inflammation with a high fat diet

ABSTRACT: The goal of this experiment was to examine the sex-dependent effect of Siah2 in brown adipose tissue

ORGANISM(S): Mus musculus

PROVIDER: GSE123990 | GEO | 2019/04/25

REPOSITORIES: GEO

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Sex-dependent effects of Siah2 on brown adipose tissue whitening and inflammation with a high fat diet

Project description:Sex-dependent effects of Siah2 on brown adipose tissue whitening and inflammation with a high fat diet

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The Ubiquitin Ligase Siah2 Regulates Obesity-induced Adipose Tissue Inflammation

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.

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Siah2 modulates sex-dependent metabolic and inflammatory responses in adipose tissue to a high-fat diet challenge.

Project description: Not available

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Siah2-dependent gene expression profile

Project description:Gene expression profiling was performed to identify Siah2-dependent changes in cells subjected to ER stress, hypoxia, and combined glucose/oxygen deprivation. To establish the magnitude of the Siah2 effect on the ER stress response, we have compared gene expression profiles of WT and Siah1a-/-::Siah2-/- mouse embryo fibroblasts (MEFs) that were subjected to glycosylation inhibitor tunicamycin (TM), thapsigargin (TG), glucose deprivation, or glucose/oxygen deprivation. Overall, this analysis confirmed changes associated with ER stress that had not previously been associated with Siah2 signaling, substantiating Siah2 as a key coordinator of ER stress through the ATF4 and sXbp1 pathways. WT and Siah1a/Siah2 KO MEF cells were treated with TM or TG for 6 h, or subjected for 12 h to oxygen deprivation, glucose deprivation or a combination of oxygen and glucose deprivation, in duplicate.

2014-04-01 | E-GEOD-39244 | biostudies-arrayexpress

Correction to: Siah2 modulates sex-dependent metabolic and inflammatory responses in adipose tissue to a high-fat diet challenge.

Project description: Not available

| S-EPMC6643305 | biostudies-literature

Siah2-dependent gene expression profile

2014-04-01 | GSE39244 | GEO

Siah2 control on tumor environment

Project description:Understanding mechanisms underlying anti-tumor immunity is pivotal for improving immune-based cancer therapies. Here we demonstrate that growth of inoculated BRAF mutant melanoma cells was inhibited in Siah2-/- mice, up to a complete loss. Melanoma grown in Siah2-/- mice exhibited increased proinflammatory immune components, signified by enhanced intra-tumoral activated T cells, along with decreased expression of Ccl17 and Ccl22, and decreased Foxp3 expression. A marked reduction in Treg proliferation was associated with inhibition of Treg cell cycle progression. Correspondingly, G1 cell cycle arrest in Siah2-/- Tregs coincided with elevated expression of the cyclin dependent kinase inhibitor p27, a Siah2 substrate. Growth of PD1-unresponsive melanoma was effectively inhibited up to complete tumor rejection in Siah2-/- mice subjected to PD1 blockade, highlighting synergy between PD1 inhibition and Siah2 loss. Siah2 regulation of Treg recruitment and cell cycle progression effectively controls melanoma development and confers synthetic lethality when combined with anti-PD1 therapy.

2019-07-18 | GSE134412 | GEO

DNA methylation alternations in the offspring brown adipose tissue from high fat diet dams

Project description:Maternal high fat diet may disturb susceptibility in offspring. Brown adipose tissue from maternal high fat diet has CpG sites that exhibit differential DNA methylationregulated compared to control.

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Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice.

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Gene expression profiles reveal the effect of a high-fat diet in brown fat development

Project description:Genome-scale analysis of the genetic factors that govern the development of white and brown adipose tissue is still far from complete. In order to identify the key genes that regulate the development of white and brown adipose tissue in mice, the transcriptome analysis was performed on adipose tissues

2015-01-08 | GSE64718 | GEO

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