AGMO Inhibitor Reduces 3T3-L1 Adipogenesis.
Ontology highlight
ABSTRACT:
SUBMITTER: Fischer C
PROVIDER: S-EPMC8147360 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated series of events including clonal expansion, growth arrest, and terminal differentiation. The mechanisms coordinating these different steps are not yet fully understood. Here we investigated whether microRNAs (miRNAs) play a role in this process. Microarray analysis was performed to detect miRNA expression during 3T3-L1 preadipocyte differentiation. Several miRNAs, including let-7, were up-regulated during 3T3-L1 adipogenesis. Ectopic introduction of let-7 into 3T3-L1 cells inhibited clonal expansion as well as terminal differentiation. The mRNA encoding high-mobility group AT-hook 2 (HMGA2), a transcription factor that regulates growth and proliferation in other contexts, was inversely correlated with let-7 levels during 3T3-L1 cell adipogenesis, and let-7 markedly reduced HMGA2 concentrations. Knockdown of HMGA2 inhibited 3T3-L1 differentiation. These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation.
| S-EPMC2691679 | biostudies-literature
Project description:Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanche that promotes the adipogenesis of 3T3-L1 preadipocytes was proved by using MTT spectrophotometry, Nile Red staining, Oil Red O staining and transcriptome sequencing technology. The mRNA level of key transcription factors for adipogenesis such as PPAR, AP2 and LPL were examined by RT-PCR. The results showed that the intracellular lipid content in cistanche treated cells were notably increased when compared with the non-treated cells. Between the differentiation and cistanche treated groups, the expression of adipogenesis related genes such as grow hormone releasing hormone (Ghrp), BCL2/adenovirus E1B interacting protein 3 (Bnip3) and Gastric inhibitory polypeptide receptor (Gipr) were significantly increased. Our findings also verified that cistanche promoted adipogenesis, which was accompanied by up-regulated level of Bnip3 and PPAR. This study could uncover new signaling pathways involved in adipogenesis regulation.
| S-EPMC8887766 | biostudies-literature
Project description:We discovered a unique expression pattern of two histone methyltransferases Suv39h1 and Suv39h2 during 3T3-L1 adipogenesis, both of which preferentially catalyse the formation of H3K9 dimethylation (H3K9me2) and further H3K9 trimethylation (H3K9me3), a transcriptional repressive mark. The expression of Suv39h1 and Suv39h2 displayed a sharp increase at the early stage of 3T3-L1 differentiation, which peaked after differentiation induction, and then declined towards later stage of differentiation, suggesting a key role for these two histone methyltransferases in adipogenesis. Indeed, inactivating Suv39h1 or Suv39h2 via lentiviral shRNA knockdown inhibited adipogenesis, while overexpressing Suv39h1 promoted adipogenesis. Notably, overexpressing or knocking down Suv39h1 in 3T3-L1 cells was associated with reciprocal changes in the expression of Wnt10a, an anti-adipogenic regulator. Further, Wnt10a knockdown largely prevented the inhibitory effect of Suv39h1 on adipogenesis, indicating Wnt10a as a downstream target mediating Suv39h1's action in adipogenesis. Mechanistically, our comprehensive approaches involving ChIP, co-immunoprecipitation and pyrosequencing analysis demonstrated that Suv39h1 may regulate Wnt10a expression via H3K9 methylation and interaction with DNA methyltransferase 1 (DNMT1) at the Wnt10a promoter, resulting in altered DNA methylation at the promoter. We conclude that Suv39h promotes adipogenesis by epigenetically down-regulating Wnt10a expression via H3K9me3 and DNA methylation at the Wnt10a promoter.Abbreviated title: Suv39h and 3T3-L1 Adipogenesis.
| S-EPMC7469483 | biostudies-literature
Project description:Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations. In addition, manipulation of AGMO in macrophages led to significant changes in the cellular lipidome, and alkylglycerolipids, the preferred substrates of AGMO, were shown to accumulate in mature adipocytes. Here, we investigated the roles of AGMO in lipid metabolism by studying 3T3-L1 adipogenesis. AGMO activity was induced over 11 days using an adipocyte differentiation protocol. We show that RNA interference-mediated knockdown of AGMO did not interfere with adipocyte differentiation or affect lipid droplet formation. Furthermore, lipidomics revealed that plasmalogen phospholipids were preferentially accumulated upon Agmo knockdown, and a significant shift toward longer and more polyunsaturated acyl side chains of diacylglycerols and triacylglycerols could be detected by mass spectrometry. Our results indicate that alkylglycerol catabolism has an influence not only on ether-linked species but also on the degree of unsaturation in the massive amounts of triacylglycerols formed during in vitro 3T3-L1 adipocyte differentiation.
| S-EPMC9192799 | biostudies-literature
Project description:Perfluorobutanesulfonic acid (PFBS) is used as the replacement of perfluorooctanesulfonic acid (PFOS) since 2000 because of the concern on PFOS' persistence in the environment and the bioaccumulation in animals. Accumulating evidence has shown the correlation between the exposure to perfluorinated compounds and enhanced adipogenesis. There is no report, however, of the effect of PFBS on adipogenesis. Therefore, the present work aimed to investigate the role of PFBS in adipogenesis using 3T3-L1 adipocytes. PFBS treatment for 6 days extensively promoted the differentiation of 3T3-L1 preadipocytes to adipocytes, resulting in significantly increased triglyceride levels. In particular, the treatments of PFBS at the early adipogenic differentiation period (day 0-2) were positively correlated with increased the triglyceride accumulation on day 6. PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein ? (C/EBP?) and peroxisome proliferator-activated receptor gamma (PPAR?), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. PFBS significantly activated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) after 4-h treatment, and PFBS' effect on triglyceride was abolished by U0126, a specific MAPK/ERK kinase (MEK) inhibitor. In conclusion, PFBS increased the adipogenesis of 3T3-L1 adipocytes, in part, via MEK/ERK-dependent pathway.
| S-EPMC6169790 | biostudies-literature
Project description:Exposure to endocrine disrupting chemicals is an established risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the potential of glyphosate, 2, 4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE) to induce lipid accumulation in murine 3T3-L1 adipocytes. Only QpE caused a dose-dependent statistically significant triglyceride accumulation from a concentration of 5 up to 100 µM. The QpE commercial formulation Targa Super was 100 times more cytotoxic than QpE alone. Neither the estrogen receptor antagonist ICI 182, 780 nor the glucocorticoid receptor antagonist RU486 was able to block the QpE-induced lipid accumulation. RNAseq analysis of 3T3-L1 adipocytes exposed to QpE suggests that this compound exerts its lipid accumulation effects via a peroxisome proliferator-activated receptor gamma (PPARγ)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPARγ reporter gene assay at 100 µM, reaching 4% of the maximal response produced by rosiglitazone, which acts as a positive control. This indicates that lipid accumulation induced by QpE is only in part caused by PPARγ activation. The lipid accumulation capability of QpE we observe suggest that this pesticide, whose use is likely to increase in coming years may have a hitherto unsuspected obesogenic property.
| S-EPMC6657571 | biostudies-literature
Project description:Recent studies have demonstrated that a number of environmental contaminants can act as metabolic disruptors and modulate metabolic function both in vitro and in vivo. 3T3-L1 mouse preadipocytes are commonly utilized to assess perturbations to adipogenesis, providing insight into environmental contaminants that may impact in vivo metabolic health. This study sought to assess whether various alkylphenol ethoxylates and alcohol ethoxylates (APEOs and AEOs, respectively), ubiquitous contaminants used in common household products, could disrupt metabolic health. 3T3-L1 cells were exposed to increasing concentrations of individual ethoxylated surfactants and base hydrophobes, and assessed for triglyceride accumulation (relative to a rosiglitazone-induced maximum response) and preadipocyte proliferation (relative to a differentiated vehicle control). We report herein that nonionic APEOs and AEOs promoted triglyceride accumulation and/or preadipocyte proliferation in 3T3-L1 cells at concentrations from 0.1 to 10 μM. Activity appeared to be an effect of the polyethoxylate chain length, as the alkylphenol/alcohol hydrophobes exhibited minimal or no adipogenic activity. In addition, nonylphenol ethoxylates (NPEO) of various ethoxylate chain lengths exhibited biphasic adipogenic activity, with increasing triglyceride accumulation and preadipocyte proliferation from NPEO (0, average ethoxylate number) through NPEO (4), and then decreasing activities from NPEO (4) through NPEO (20). Our results suggest potential metabolic impacts of these compounds at environmentally relevant concentrations, demonstrating a need to further assess molecular mechanisms and better characterize environmental concentrations of the specific AEOs and APEOs that are inducing the greatest degree of adipogenic activity herein.
| S-EPMC6256959 | biostudies-literature
Project description:Flubendiamide, a ryanoid class insecticide, is widely used in agriculture. Several insecticides have been reported to promote adipogenesis. However, the potential influence of flubendiamide on adipogenesis is largely unknown. The current study was therefore to determine the effects of flubendiamide on adipogenesis utilizing the 3T3-L1 adipocytes model. Flubendiamide treatment not only enhanced triglyceride content in 3T3-L1 adipocytes, but also increased the expression of cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ, two important regulators of adipocyte differentiation. Moreover, the expression of the most important regulator of lipogenesis, acetyl coenzyme A carboxylase, was also increased after flubendiamide treatment. Further study revealed that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or A769662, two Adenosine 5'-monophosphate (AMP)-activated protein kinase α activators, subverted effects of flubendiamide on enhanced adipogenesis. Together, these results suggest that flubendiamide promotes adipogenesis via an AMPKα-mediated pathway.
| S-EPMC6278525 | biostudies-literature
Project description:3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogeneic media. Two technical replicates from four time points relative to induction of adipogenesis (day 0)
2010-09-30 | E-GEOD-20696 | biostudies-arrayexpress
Project description:3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogenic media. Examination of 6 histone modifications and CTCF at 4 time points and PPARG at 1 time point using ChIP-Seq
2010-09-30 | E-GEOD-21365 | biostudies-arrayexpress