Gene expression profile of developing adipose tissue in vivo
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29502 | GEO | 2011/12/08
SECONDARY ACCESSION(S): PRJNA141385
REPOSITORIES: GEO
Similar Datasets
Project description:Obesity is characterized by an increase in the size and the number of adipocytes. However, the mechanisms responsible for the formation of adipocytes during development and the molecular mechanisms regulating their increase and maintenance in adulthood are poorly understood. Here, we report the use of leptin-luciferase BAC transgenic mice to track white adipose tissue (WAT) development and guide the isolation and molecular characterization of adipocytes during development using DNA microarrays. These data reveal distinct transcriptional programs that are regulated during murine WAT development in vivo. Developing mouse adipose tissue from at least 3 embryos were pooled for embryonic and postnatal time points.
2011-12-08 | E-GEOD-29502 | biostudies-arrayexpress
Project description:Leptin expression decreases after fat loss and is increased when obesity develops and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer (LE1), 16kb upstream from the transcription start site (TSS), confers fat-specific expression in a BAC transgenic reporter mouse (BACTG). However this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass. In this report, we used ATAC-seq to identify a 17bp non-canonical-PPARγ/RXRα-binding site leptin regulatory element 1 (LepRE1) within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) expression. While BACTG reporter mice with mutations in this sequence still show fat-specific expression, luciferase is no longer decreased after food restriction and weight loss. Similarly the increased expression of leptin reporter associated with obesity in ob/ob mice is impaired. A functionally analogous LepRE1 site is also found in a second, redundant DNA regulatory element 13kb downstream of the TSS. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid sensing system in adipocytes.
2018-06-11 | GSE113413 | GEO
Project description:Background: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. Fsp27 is expressed in both BAT and WAT and promotes lipid storage and the development of obesity and diabetes. In addition, Fsp27-deficient white adipocytes acquired certain BAT-like properties including reduced lipid droplet size and increased mitochondrial activity. Using microarray and semi-quantitative real-time PCR analyses, we systematically analyzed the gene expression profile in Fsp27-deficient WAT and BAT. Results: We observed that BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of Fsp27-/- mice. Expression levels of BAT-selective genes were also dramatically up-regulated in the WAT of leptin and Fsp27 double deficient mice. Furthermore, we observed that expression levels of genes in multiple metabolic pathways including oxidative phosphorylation, the TCA cycle and fatty acid synthesis and oxidation were increased in the Fsp27-/- WAT. In contrast, expression levels for extracellular matrix remodeling, the classic complement pathway and TGF-β signaling"were down-regulated in the WAT of Fsp27-/- mice. Most importantly, regulatory factors that determine BAT identity such as CEBPα/β, PRDM16 and major components in the cAMP pathway were markedly up-regulated in the WAT of Fsp27-/- mice. Interestingly, we observed distinct gene expression profiles in the BAT of Fsp27-/- mice. Conclusion: Our data suggest that Fsp27 acts at upstream to control gene expression of diverse pathways, in particular the expression of regulatory factors that determine the identity of BAT and WAT. Therefore, Fsp27 is an important molecular determinant for the identity of WAT, and loss of Fsp27 leads to the conversion of WAT to a BAT-like tissue. Total RNAs were extracted from individual gonadal WAT of five pairs of 3-month-old wild-type and Fsp27-null male mice. Equal amounts of RNA from five pairs of mice with each genotype were pooled to form RNA pools (total 45 μg). Duplicate experiments were carried out.
2010-07-07 | E-GEOD-22693 | biostudies-arrayexpress
Project description:Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that transcriptional coregulators YAP and TAZ mediate the crosstalk between fat mass and leptin levels to maintain metabolic homeostasis. Activating YAP/TAZ in adipocytes by Lats1 and Lats2 deletion results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells. Surprisingly, Lats1/2 knockout mice did not exhibit lipodystrophy-related metabolic dysfunction, attributed to a paradoxical increase in circulating leptin levels. Mechanistically, YAP/TAZ-TEAD signaling upregulates leptin expression by directly binding an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is linked to, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ plays an essential role in coordinating adipose storage capacity and systemic energy balance through dual control of adipocyte plasticity and leptin gene transcription.
2024-03-21 | GSE261825 | GEO
Project description:Decreased ambient temperature, from birth to weaning, significantly reduced fat mass (FM) and adiposity in developing mice. Changes in FM content in 10 day-old mice raised at 17°C were not accompanied by precocious induction of brown adipocytes in inguinal white adipose tissue (WAT). Brown phenotype was induced in 21 day-old mice independently of ambient temperature (17°C or 29°C) however the expression of Ucp1 and other brown fat biomarker genes was greater in animals raised at 17°C suggesting increased adaptive thermogenesis. Accordingly, we predict that the induction of brown adipocytes in WAT follows a strict developmental program and the number of potential brown adipocytes in WAT is determined genetically. Microarray analysis of gene expression was performed on inguinal white adipose tissue dissected from 10 and 21 day-old mice kept at different temperature conditions, that is, in mice maintained at 17°C or 29oC during early post-natal development.
2015-05-03 | E-GEOD-62350 | biostudies-arrayexpress
Project description:Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders. We used microarrays to identify global gene expression in 3T3-L1 adipocytes lacking TBLR1 and compared gene expression to control shRNA treated cells in both basal and isoproterenol stimulated states. We analyzed 12 RNA samples extracted from 3T3-L1 adipocytes that were treated with either control or TBLR1 specific shRNAs and with or without 10 µM isoproterenol for 3 hrs. Three replicates of each condition.
2013-04-01 | E-GEOD-43658 | biostudies-arrayexpress
Project description:The differentiation of preadipocytes into adipocytes is controlled by several transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are known as master regulators of adipogenesis. BCL11B is a zinc finger-type transcription factor that regulates the development of the skin and central nervous and immune systems. Here, we found that BCL11B was expressed in the white adipose tissue (WAT), particularly the subcutaneous WAT and that BCL11Bâ/â mice had a reduced amount of subcutaneous WAT. During adipogenesis, BCL11B expression transiently increased in 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). The ability for adipogenesis was reduced in BCL11B knockdown 3T3-L1 cells and BCL11Bâ/â MEFs, whereas the ability for osteoblastogenesis was unaffected in BCL11Bâ/â MEFs. Luciferase reporter gene assays revealed that BCL11B stimulated C/EBPβ activity. Furthermore, the expression of downstream genes of the Wnt/β-catenin signaling pathway was not suppressed in BCL11Bâ/â MEFs during adipogenesis. Thus, this study identifies BCL11B as a novel regulator of adipogenesis, which works, at least in part, by stimulating C/EBPβ activity and suppressing the Wnt/β-catenin signaling pathway. MEFs were derived from embryonic day 12.5 BCL11B+/+ and BCL11Bâ/â C57BL6 mice embryos. After 2 times passage, MEFs were differentiated using the adipocyte differentiation medium and 10 μM pioglitazone. After 12 h of adipocyte differentiation, gene expression profiles were analyzed by DNA microarray.
2016-09-05 | E-GEOD-83980 | biostudies-arrayexpress
Project description:The differentiation of preadipocytes into adipocytes is controlled by several transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are known as master regulators of adipogenesis. BCL11B is a zinc finger-type transcription factor that regulates the development of the skin and central nervous and immune systems. Here, we found that BCL11B was expressed in the white adipose tissue (WAT), particularly the subcutaneous WAT and that BCL11B−/− mice had a reduced amount of subcutaneous WAT. During adipogenesis, BCL11B expression transiently increased in 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). The ability for adipogenesis was reduced in BCL11B knockdown 3T3-L1 cells and BCL11B−/− MEFs, whereas the ability for osteoblastogenesis was unaffected in BCL11B−/− MEFs. Luciferase reporter gene assays revealed that BCL11B stimulated C/EBPβ activity. Furthermore, the expression of downstream genes of the Wnt/β-catenin signaling pathway was not suppressed in BCL11B−/− MEFs during adipogenesis. Thus, this study identifies BCL11B as a novel regulator of adipogenesis, which works, at least in part, by stimulating C/EBPβ activity and suppressing the Wnt/β-catenin signaling pathway.
2016-09-05 | GSE83980 | GEO
Project description:We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (snATAC-seq) characterization of cellular subtypes (adipose stromal cells (ASC) and adipocyte nuclei) during inguinal WAT (subcutaneous; iWAT) development in mice, capturing the early postnatal period (postnatal days (PND) 06 and 18) through adulthood (PND56).
2021-09-08 | GSE180589 | GEO
Project description:B cell-activating factor (BAFF) is critical for the survival and maturation of B2 cells. However, excess BAFF breaks the peripheral tolerance of B2-cells leading to the production of autoantibodies that cause autoimmune diseases. During obesity, BAFF is predominantly produced by white adipose tissue (WAT), and IgG autoantibodies against adipocytes are identified in the WAT of obese humans. However, it remains to be determined if the autoantibodies formed during obesity affect WAT remodeling and systemic insulin resistance. Here, we show that IgGs from high-fat diet (HFD)-induced obese mice bind to apoptotic adipocytes and promote their clearance by macrophages. Next, using murine models of obesity in which the gonadal WAT undergoes remodeling, unexpectedly we found that BAFF neutralization increased the number of dead adipocytes and exacerbated WAT inflammation and insulin resistance despite depletion of IgG autoantibodies. RNA sequencing of the stromal vascular fraction from the WAT revealed impaired B cell activation and phagocytosis pathways. In-vitro, the clearance of apoptotic adipocytes by macrophages was attenuated in the presence of IgGs from BAFF-neutralized mice compared to the control mice. Altogether, our study suggests a beneficial role of BAFF and IgG autoantibodies in WAT remodeling in obesity and the regulation of systemic insulin resistance.
2024-08-28 | GSE255950 | GEO