Translational control in early adipogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29744 | GEO | 2012/03/29
SECONDARY ACCESSION(S): PRJNA141175
REPOSITORIES: GEO
Similar Datasets
Project description:In obesity, adipose tissue expands by increasing the volume of existing adipocytes (hypertrophy), increasing the number of small adipocytes (hyperplasia) or both. Much is known about transcriptional control during adipogenesis, including early events. However, translational control plays a pivotal role in many dynamic processes and we presume that it is also important for the control of adipogenesis, especially in the first hours after hormonal induction. By use of ribosome profiling we identified 43 genes that are up-regulated and 2 genes that are down-regulated during the first six hours of adipogenesis in 3T3-L1 cells. Interestingly, we found Ghrelin to be down-regulated. Up-regulated genes comprise factors that are nucleic acid binding (Cdkn1c, eIF4b, Hsf1, Irf6, Myc, Plekhn1, Polr2a, Rpl18, Rpl27a, Rpl6, Rpl7a, Rps18, Rpsa, Sema3g, Tbc1d22a, Tsc22d3), form part of ribosomes (L6, L7a, L18, L27a, Sa, S18, S15a pseudogene), act on the regulation of translation (eIF4b) or transcription (Hsf1, Irf6, Myc, Tsc22d3). Others act as chaperones (Bag3, Hspa8/Hsc70, Hsp90ab1) or in other metabolic or signals transducing processes. We conclude that a moderate reorganisation of the functionality of the ribosomal machinery is a very important step for the growth and expression control at the beginning of adipogenesis. 12 samples: 4 (0h, non-polysomal fraction; 0h, polysomal fraction; 6h, non-polysomal fraction; 6h, polysomal fraction) x3 replicates
2012-03-28 | E-GEOD-29744 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE27912: Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity (Exiqon) GSE27949: Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity (Affymetrix) Refer to individual Series
2011-06-10 | E-GEOD-27951 | biostudies-arrayexpress
Project description:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity. 3 samples of pre adipocytes isolated from brown adipose tissue examined pre and post differentiation to brown adipocytes. 3 samples of pre-adipocytes isolated from white adipose tissue and examined pre and post differentiation to adipocytes.
2011-05-31 | E-GEOD-27912 | biostudies-arrayexpress
Project description:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity. A global transcriptomic survey of subcutaneous adipose tissue from human subjects characterised as having normal glucose tolerance, glucose intolerance or frank type 2 diabetes.
2011-05-31 | E-GEOD-27949 | biostudies-arrayexpress
Project description:Recents studies in mice and humans demonstrated the relevance of H2S-synthesising enzymes (such as CTH, CBS and MPST) in adipose tissue physiology and preadipocyte differentiation into adipocytes. Here, we aimed to investigate the combined role of CTH, CBS and MPST in the preservation of adipocyte protein persulfidation and adipogenesis. Joint CTH, CBS and MPST gene knockdown was achieved treating fully human adipocytes with siRNAs against these transcripts (siRNA_MIX). Adipocyte protein persulfidation was analyzed by a mass spectrometry label-free quantitative approach coupled with a dimedone-switch method for protein labeling and purification. The proteomic analysis quantified 216 proteins with statistically different persulfidation levels in KD cells compared to control adipocytes. In fully differentiated adipocytes, CBS and MPST mRNA and protein levels were abundant, whereas CTH expression was very low. Of note, siRNA_MIX administration resulted in a significant decrease in CBS and MPST expression, without impacting on CTH. Dual CBS and MPST gene knockdown resulted in decreased expression of relevant genes for adipocyte biology, including adipogenesis, mitochondrial biogenesis and lipogenesis, but increased proinflammatory- and senescence-related genes, in parallel to a significant disruption in adipocyte protein persulfidation pattern. While among less persulfidated proteins, we identified several relevant proteins for adipocyte adipogenesis and function, among the most persulfidated, key mediators of adipocyte inflammation and dysfunction, but also some proteins that might have a positive role of adipogenesis were found. In conclusion, current study indicates that joint knockdown of CBS and MPST (but not CTH) in adipocytes impairs adipogenesis and promotes inflammation, possibly by disrupting the pattern of protein persulfidation in these cells, and suggesting that these enzymes were required for the functional maintenance of adipocytes.
2022-08-12 | PXD032370 | Pride
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:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity.
2011-05-31 | GSE27912 | GEO
Project description:Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity.
2011-05-31 | GSE27949 | GEO
Project description:Obesity is a major health burden. Adipogenesis, the proliferation and differentiation of pree-adipocytes in mature adipocytes, could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases, blocks adipogenesis. New allelic variants of SIRT6 (N308K/A313S) were recently associated with the longevity in Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level. Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner.
2024-08-10 | PXD051761 | Pride
Project description:The tumor microenvironment, including adipocytes, is a critical element for breast cancer (BC) progression, also responding to metabolic stimuli characterizing obesity and/or diabetes. The reciprocal reprogramming established between BC cells and adipocytes remains to be deciphered. We investigated (i) the effect of mammary adipocytes on BC cells and vice versa, (ii) the impact of glucose on BC cells, adipocytes and (iii) the impact of glucose on their cross-talk. We have identified adipocyte-modulated genes in BC cells and BC cell-modulated genes in adipocytes, dependently and independently of glucose levels. We identified the adipogenesis process as the most relevantly differentially regulated pathway both in cancer cells and in adipocytes upon exposure to high glucose concentration. Specifically, we observed that BC cells promote de-differentiation of adipocytes and re-shaping toward a fibroblast-like phenotype, particularly upon glucose lowering; the de-lipidation of adipocytes is paralleled by induction of adipogenesis genes in BC cells.
2024-09-19 | GSE243555 | GEO