Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA401789 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Brown adipose tissue plays a crucial role in modulating whole-body energy expenditure through the thermogenic function of its mitochondrial respiratory chain. Pharmacological interventions targeting this function hold significant therapeutic promise. Thus, gaining a comprehensive understanding of the pathophysiological regulation of brown adipose tissue is imperative for future therapeutic applications. In this study, we investigated the metabolic mechanisms underlying the regulation of mature brown adipocyte function by the mitochondrial respiratory chain. Our findings indicate that deficiency in mitochondrial complex I in mature brown adipocytes leads to lipidomic remodeling. This remodeling results in an increase in arachidonic acid content and prostaglandin E2 (PGE2) production, leading to reduced transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor alpha (PPARα) and alterations in the content of PPAR activator complexes, which consequently result in reduced brown adipocyte thermogenesis and peroxisomal gene expression in mature brown adipocyte. In summary, our study elucidates that the mitochondrial-derived arachidonic acid signal regulates brown adipocyte thermogenesis and peroxisome biogenesis by modulating the PPAR activator complex."
2024-05-03 | GSE266292 | GEO
Project description:Here we have characterized the transcriptional processes underlying the formation of human brown in white (i.e. brite) adipocytes using a genome-wide approach. We show that the browning process is associated with reprogramming of peroxisome proliferator-activated receptor γ (PPARγ) binding to form brite adipocyte-selective PPARγ super-enhancers that appear to play a key role in activation of brite adipocyte-selective genes. We identify the KLF11 gene based on its association with a PPARγ super-enhancer and show that KLF11 is a novel browning factor directly induced by rosiglitazone and required for the activation of brite adipocyte-selective gene program by rosiglitazone.
2014-12-12 | GSE59703 | GEO
Project description:Here we have characterized the transcriptional processes underlying the formation of human brown in white (i.e. brite) adipocytes using a genome-wide approach. We show that the browning process is associated with reprogramming of peroxisome proliferator-activated receptor γ (PPARγ) binding to form brite adipocyte-selective PPARγ super-enhancers that appear to play a key role in activation of brite adipocyte-selective genes. We identify the KLF11 gene based on its association with a PPARγ super-enhancer and show that KLF11 is a novel browning factor directly induced by rosiglitazone and required for the activation of brite adipocyte-selective gene program by rosiglitazone. Genome-wide profiling of Dnase I hypersenstive (DHS) sites, epigenomic marks, transcription factor and co-factor binding, and gene expression in hMADS white and brite adipocytes
2014-12-12 | E-GEOD-59703 | biostudies-arrayexpress
Project description:Peroxisome proliferator‑activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation, however their role in regulating brown fat functionality has not been resolved. To address this question, we generated inducible brown fat specific mouse models for PPARa, b/d and g, respectively. Interestingly, we found that both PPARa and b/d are dispensable for brown fat function. In contrast, we could show that ablation of PPARg in vitro as well in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARgfunction, and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARg mediated regulation of brown fat function and activation by β-adrenergic signaling.
2018-01-16 | GSE103474 | GEO
Project description:Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1β, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a previously unknown brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.
2023-08-23 | GSE235476 | GEO
Project description:Glycerol kinase (GK) is at the interface of fat and carbohydrate metabolism and has been implicated in insulin resistance and type 2 diabetes mellitus (T2DM). To define GK’s role in insulin resistance, we examined gene expression in brown adipose tissue in a glycerol kinase (Gyk) knockout (KO) mouse model using microarray analysis. Global gene expression profiles of KO mice were distinct from wild type (WT) with 668 genes that were differentially expressed. These included genes involved in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Real-Time (RT) PCR analysis confirmed the differential expression of selected genes involved in lipid and carbohydrate metabolism. PathwayAssist analysis confirmed direct and indirect connections between GK and genes in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Network Component Analysis (NCA) showed that the transcription factors, peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory element binding factor 1 (SREBP-1), SREBP-2, signal transducer and activator of transcription 3 (STAT3), STAT5, trans-acting transcription factor 1 (SP1), CCAAT/enhancer binding protein alpha (CEBP-α), cAMP responsive element binding protein 1 (CREB), glucocorticoid receptor (GR), and PPAR-α have altered activity in the KO mice. NCA also revealed the individual contribution of these transcription factors on the expression of genes altered in the microarray data. This study elucidates the transcription network of Gyk and further confirms a role for Gyk, a simple Mendelian disorder, in insulin resistance and T2DM, a common complex genetic disorder. Keywords: genotype state analysis
2007-03-11 | GSE4656 | GEO
Project description:Glycerol kinase (GK) is at the interface of fat and carbohydrate metabolism and has been implicated in insulin resistance and type 2 diabetes mellitus (T2DM). To define GK's role in insulin resistance, we examined gene expression in brown adipose tissue in a glycerol kinase (Gyk) knockout (KO) mouse model using microarray analysis. Global gene expression profiles of KO mice were distinct from wild type (WT) with 668 genes that were differentially expressed. These included genes involved in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Real-Time (RT) PCR analysis confirmed the differential expression of selected genes involved in lipid and carbohydrate metabolism. PathwayAssist analysis confirmed direct and indirect connections between GK and genes in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Network Component Analysis (NCA) showed that the transcription factors, peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory element binding factor 1 (SREBP-1), SREBP-2, signal transducer and activator of transcription 3 (STAT3), STAT5, trans-acting transcription factor 1 (SP1), CCAAT/enhancer binding protein alpha (CEBP-α), cAMP responsive element binding protein 1 (CREB), glucocorticoid receptor (GR), and PPAR-α have altered activity in the KO mice. NCA also revealed the individual contribution of these transcription factors on the expression of genes altered in the microarray data. This study elucidates the transcription network of Gyk and further confirms a role for Gyk, a simple Mendelian disorder, in insulin resistance and T2DM, a common complex genetic disorder. Experiment Overall Design: 7 samples are analyzed; 3 wildtype and 4 KO. the WT samples are used as control and KO samples are used as the experimental group.
2007-11-22 | E-GEOD-4656 | biostudies-arrayexpress
Project description:Interventions: primary colorectal cancer group VS healthy control group:no intervention
Primary outcome(s): Peroxisome proliferator-activated receptor delta-87T>C
Study Design: Factorial
| 35322 | ecrin-mdr-crc
Project description:Pharmacological activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) is a convenient and promising tactic for promoting beige adipocyte biogenesis to combat obesity-related metabolic disorders. However, thiazolidinediones (TZDs), the full agonist of PPAR-γ exhibits severe side effects in animal model and clinical uses. Therefore, it is emerging to develop efficient and safe PPAR-γ modulators for metabolic disease treatment. Here, by utilizing comprehensive methods, we report a previously unidentified ligand binding pocket (LBP) in PPAR-γ and link it to beige adipocyte differentiation. Further virtual screening from 4097 natural compounds based on this novel LBP, we discover NJT-2, a terpenoid compound, can bind to PPAR-γ induce co-activator recruitment and effectively activate PPAR-γ mediated transcription of beige adipocyte program. Importantly, in mouse model, NJT-2 administration efficiently promotes beige adipocyte biogenesis and improve obesity-associated metabolic dysfunction with significant lower adverse effects than those observed in TZD. Our results not only provide an advanced molecular insight into the structural ligand binding details in PPARg, but also develop its linked selective and safe agonist for obesity treatment.
2024-05-21 | GSE267657 | GEO
Project description:To identify novel Peroxisome Proliferator-Activated Receptor gamma (PPARg) responsive secretory and/or transmembrane genes that is related to obesity, we integrated the expression data from the adipose tissue derived from obese mice with the other two data sets: expression profiling of adipocyte differentiation using ST2 cells and siRNA-mediated knockdown of Pparg during ST2 cell adipogenesis. We used microarrays to detect the up-regulated genes in adipose tissue derived from mice fed a high fat diet compared to a control.
2013-01-30 | GSE36492 | GEO