Effects of rosiglitazone treatment on lipid composition
Ontology highlight
ABSTRACT:
ORGANISM(S): Human Homo Sapiens
TISSUE(S): Adipose Tissue
SUBMITTER: 
Maureen Kachman
PROVIDER: ST000675 | MetabolomicsWorkbench | Mon Jun 05 00:00:00 BST 2017
REPOSITORIES: MetabolomicsWorkbench
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Project description:Reprograming of 'white' to 'brite' adipocytes with higher oxidative capacity and improved endocrine function represents a potentially important approach to address the dysfunctional adipocyte phenotypes in obesity. We find that chronic treatment with the PPAR? agonist (rosiglitazone, 1 uM for 7days in vitro) in white human adipose tissue induced metabolic changes. Our trancriptome analysis showed that higher mitochondrial and peroxisomal fatty acid oxidation pathways and other genes involved in lipid metabolism including (re)esterification are induced by rosiglitazone treatment. To understand the biochemical basis of brite vs. white human adipocytes, we will perform comprehensive metabolomic profiling of control and rosiglitazone treated tissues using unbiased lipidomics approach.
2018-08-02 | MSV000082717 | GNPS
Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBP? in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBP?, as a lipogenic transcription factor, has unique direct targets compared to PPAR?. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBP? and PPAR? in adipocytes by short-term C/EBP? or PPAR? elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBP? and PPAR? cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBP? specific targets in mice on a chow diet, most of the C/EBP? targets in mature adipocytes are genes modulated by HFD feeding. Total RNA obtained from subcutaneous adipose tissue of Adn-C/EBP?-/- mice on doxycycline chow diet for 3 days, doxycycline high fat diet for 3 days or 1 month and Adn-PPAR?-/- mice on doxycycline chow diet for 3 days, compared to control littermates.
2014-11-04 | E-GEOD-62937 | biostudies-arrayexpress
Project description:The nuclear receptor PPAR gamma is required for adipocyte differentiation, but its role in mature adipocytes is less clear. Here we report that knockdown of PPAR gamma expression in 3T3-L1 adipocytes returned the expression of most adipocyte genes towards preadipocyte levels. Consistently, down regulated but not up regulated genes showed strong enrichment of PPAR gamma binding. Surprisingly, not all adipocyte genes were reversed and the adipocyte morphology was maintained for an extended period after PPAR gamma depletion. To explain this, we focused on transcriptional regulators whose adipogenic regulation was not reversed upon PPAR gamma depletion. We identified GATA2, a transcription factor whose down-regulation early in adipogenesis is required for preadipocyte differentiation, remaining low after PPAR gamma knockdown. Forced expression of GATA2 in mature adipocytes complemented PPAR gamma depletion and impaired adipocyte functionality with a more preadipocyte- like gene expression profile. Ectopic expression of GATA2 in adipose tissue in vivo had similar effect on adipogenic gene expression. These results suggest that PPAR gamma-independent down regulation of GATA2 prevents reversion of mature adipocytes after PPAR gamma depletion. Experiment Overall Design: This dataset consists of three sample groups: preadipocytes, control siRNA treated adipocytes, and PPAR gamma siRNA treated adipocytes. Each sample group consists of three replicates samples. Each sample was hybridized to a separate array for a total of nine arrays. Experiment Overall Design: Technical replicates: Pread 1, Pread 2, Pread 3 Experiment Overall Design: Technical replicates: Cont siRNA 1, Cont siRNA 2, Cont siRNA 3 Experiment Overall Design: Technical replicates: PPAR gamma siRNA 1, PPAR gamma siRNA 2, PPAR gamma siRNA 3
2009-01-29 | E-GEOD-14004 | biostudies-arrayexpress
Project description:The nuclear receptor PPAR gamma is required for adipocyte differentiation, but its role in mature adipocytes is less clear. Here we report that knockdown of PPAR gamma expression in 3T3-L1 adipocytes returned the expression of most adipocyte genes towards preadipocyte levels. Consistently, down regulated but not up regulated genes showed strong enrichment of PPAR gamma binding. Surprisingly, not all adipocyte genes were reversed and the adipocyte morphology was maintained for an extended period after PPAR gamma depletion. To explain this, we focused on transcriptional regulators whose adipogenic regulation was not reversed upon PPAR gamma depletion. We identified GATA2, a transcription factor whose down-regulation early in adipogenesis is required for preadipocyte differentiation, remaining low after PPAR gamma knockdown. Forced expression of GATA2 in mature adipocytes complemented PPAR gamma depletion and impaired adipocyte functionality with a more preadipocyte- like gene expression profile. Ectopic expression of GATA2 in adipose tissue in vivo had similar effect on adipogenic gene expression. These results suggest that PPAR gamma-independent down regulation of GATA2 prevents reversion of mature adipocytes after PPAR gamma depletion. Keywords: cell type comparison, Gata2, PPAR gamma, adipocyte, preadipocytes, differentiation
2009-01-14 | GSE14004 | 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:Aims: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of Heart and neural crest derivatives-expressed protein 2 (HAND2) in adipogenesis. Methods: Human white adipose tissue (WAT) were collected in a cross-sectional study of 318 individuals. In vitro, for mechanistic experiments we used primary adipocytes from human and mice as well as human multipotent adipose derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from LoxP mouse models with Cre-encoding mRNA. Adipogenesis efficiency was measured by OilRedO staining, qPCR and microarray. A combinatorial RNASeq approach was used to identify gene clusters regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (HAND2AdipoqCRE). Results: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was required but insufficient for adipocyte differentiation in vitro. In a large cohort of humans with obesity, WAT HAND2 expression was correlated to body-mass-index (BMI). The HAND2 gene was enriched in white adipocytes compared to brown, induced early in differentiation and responded to DEX, a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by GCs via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that Hand2 was required at stages prior to Adipoq expression. Conclusion: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in human and mice.
2021-02-26 | GSE148699 | GEO
Project description:The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.
2024-09-10 | GSE242977 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
2022-05-01 | GSE175654 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
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2011-07-13 | E-GEOD-26207 | biostudies-arrayexpress