Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA151751 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized. Wild type and P2X7 knockout mice were fed a low fat diet (chow) or high fat diet for 12 weeks. After the diet intervention period, the animals were killed and epididymal white adipose tissue was removed. Total RNA was isolated and subjected to gene expression profiling.
2012-02-24 | E-GEOD-36033 | biostudies-arrayexpress
Project description:Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
2012-02-24 | GSE36033 | GEO
Project description:Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in pro-inflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3 [NLR family, pyrin domain containing 3] resulting in caspase-1 activation and production of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Here, we showed that mice deficient in Nlrp3, ASC [apoptosis-associated speck-like protein containing a CARD; a.k.a PYCARD (PYD and CARD domain containing)] and caspase-1 were resistant to the development of high fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance and suggest inhibition of the inflammasome as a potential therapeutic strategy. Keywords: Expression profiling by array Wild-type (WT), ASC-null and Casp1-null mice were subjected to high fat diet feeding for 16 weeks. After the diet intervention period, the animals were killed and epididymal white adipose tissue was removed. Total RNA was isolated and subjected to gene expression profiling.
2011-08-20 | E-GEOD-25205 | biostudies-arrayexpress
Project description:Appetite control is key to combat obesity in an over-nutritious environment. Whether and how over-nutrition induces hyperphagia and obesity through the adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues. Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake. Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of anandamide (AEA), an endogenous appetite-inducing cannabinoid (CB). Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner. These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis that induces hyperphagia and obesity.
2018-09-12 | GSE111735 | GEO
Project description:The noncanonical inflammasome induced by intracellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis, which is critical for induction of endotoxic shock in mice. However, the signaling pathway downstream of caspase-11 is unknown. We found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel followed up by ATP release, which in turn activated the purinergic P2X7 receptor to mediate cytotoxicity. In the absence of P2X7 or pannexin-1, pyroptosis induced by cytosolic LPS was abrogated. Cleavage of pannexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-mediated pyroptosis. Priming the caspase-11 pathway in vivo with LPS or Toll-like receptor-3 (TLR3) agonist resulted in high mortality in wild-type mice after secondary LPS challenge, but not in Casp11(-/-), Panx1(-/-), or P2x7(-/-) mice. These results reveal a critical role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis induced by the noncanonical inflammasome.
Research is published, core data not used but project description is relevant:
http://www.sciencedirect.com/science/article/pii/S1074761315004094
2015-06-05 | ST000174 | MetabolomicsWorkbench
Project description:Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high-fat diet (HFD) feeding, activation of NKT cells by lipid agonist α-galactosylceramide (αGalCer) enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identifies a novel therapeutic target for the treatment of obesity-associated inflammation and type-2 diabetes. Wild type and CD1d1 antigen (CD1d) knockout mice were fed a high fat diet for 4 days. On day 0 and 2 mice were injected intraperitoneally with α-galactosylceramide (αGalCer) or vehicle. On day 4 mice were killed and gene expression was profiled in epididymal adipose tissue.
2012-04-12 | E-GEOD-36032 | biostudies-arrayexpress
Project description:GRBATKO_BAT_COLDEXPOSURE Aberrant activity of the glucocorticoid (GC)/glucocorticoid receptor (GR) endocrine system has been linked to obesity-related metabolic dysfunction. Traditionally, the GC/GR axis has been believed to play a crucial role in adipose tissue formation and function in both, white (WAT) and brown adipose tissue (BAT). While recent studies have challenged this notion for WAT, the contribution of GC/GR signaling to BAT-dependent energy homeostasis remained unknown. Here, we have generated and characterized a BAT-specific GR knockout mouse (GRBATKO), for the first time allowing to genetically interrogate the metabolic impact of BAT GR. The HPA axis in GRBATKO mice was intact, as was the ability of mice to adapt to cold. BAT GR was dispensable for the adaptation to fasting-feeding cycles and the development of diet-induced obesity. In obesity, glucose and lipid metabolism, insulin sensitivity, and food intake remained unchanged, aligning with the absence of changes in thermogenic gene expression. Together, we demonstrate that the GR in UCP1-positive BAT adipocytes plays a negligible role in systemic metabolism and BAT function, thereby opposing a long-standing paradigm in the field.
2019-08-26 | GSE135544 | GEO
Project description:Toll-like receptors/Interleukin-1 receptor (IL-1R) signaling plays an important role in High-fat diet (HFD)-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM (IL-1R-associated kinase M)-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduced HFD-induced body weight gain, increased whole body energy expenditure and improved insulin resistance, associated with decreased lipid accumulation and adipocyte cell sizes. IL-1β stimulation induced the translocation of IRAKM Myddosome to mitochondria to promote de novo lipogenesis in adipocytes. Mechanistically, IRAKM interacts with and phosphorylates mitochondrial citrate carrier Slc25a1 to promote IL-1β-induced mitochondrial citrate transport to cytosol and de novo lipogenesis. Moreover, IRAKM-Slc25a1 axis mediates IL-1β induced Pgc1a acetylation to regulate thermogenic gene expression in adipocytes. IRAKM kinase-inactivation also attenuated HFD-induced obesity. Taken together, our study suggests that the IL-1R-IRAKM-Slc25a1 signaling axis tightly links inflammation and adipocyte metabolism, indicating a novel therapeutic target for obesity.
2022-06-09 | PXD031934 | Pride
Project description:Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in pro-inflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3 [NLR family, pyrin domain containing 3] resulting in caspase-1 activation and production of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Here, we showed that mice deficient in Nlrp3, ASC [apoptosis-associated speck-like protein containing a CARD; a.k.a PYCARD (PYD and CARD domain containing)] and caspase-1 were resistant to the development of high fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance and suggest inhibition of the inflammasome as a potential therapeutic strategy. Keywords: Expression profiling by array
2011-08-21 | GSE25205 | GEO
Project description:Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high-fat diet (HFD) feeding, activation of NKT cells by lipid agonist α-galactosylceramide (αGalCer) enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identifies a novel therapeutic target for the treatment of obesity-associated inflammation and type-2 diabetes.
2012-04-13 | GSE36032 | GEO