Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD- induced zebrafish
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246843 | GEO | 2023/11/02
REPOSITORIES: GEO
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Project description:Gene expression profiling to examine the effets of prieurianin in a time-course study (0, 0.25, 0.5, 1, 2, 3, 5, 9, 12, 15, 24, 36, 48, 96, 144, 192, 240, and 288 hrs) on the differentiation of the 3T3-L1 preadipocytes into adipocytes. The sharp rise in the incidence of obesity in the last two decades has become one of the most serious public health risks worldwide. Currently approved therapies for obesity exhibit modest efficacy and limiting side effects. We show here that prieurianin, a limonoid, causes weight loss by reducing energy intake in morbidly obese mice and in mice on high-calorie diet. Prieurianin is also anti-adipogenic by inhibiting the proliferation and differentiation of preadipocytes into adipocytes, and induces either dedifferentiation or delipidation of mature adipocytes. Gene expression profiling shows that prieurianin suppresses the expression of genes involved in fat metabolism, and increases the expression of a transcription repressor, zinc finger protein 68 (Zfp68), which inhibits CCAAT/enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated receptor γ (PPARγ), master transcriptional regulators of adipogenesis. The effects of prieurianin are reminiscent of several cytokines that regulate appetite and adipogenesis, and holds promise as an effective anti-obesity drug. Keywords: Time course, prieurianin, obesity, differentiation, adipogenesis, preadipocytes, adipocytes, Zfp68
2010-02-08 | GSE15018 | GEO
Project description:Gene expression profiling to examine the effets of prieurianin in a time-course study (0, 0.25, 0.5, 1, 2, 3, 5, 9, 12, 15, 24, 36, 48, 96, 144, 192, 240, and 288 hrs) on the differentiation of the 3T3-L1 preadipocytes into adipocytes. The sharp rise in the incidence of obesity in the last two decades has become one of the most serious public health risks worldwide. Currently approved therapies for obesity exhibit modest efficacy and limiting side effects. We show here that prieurianin, a limonoid, causes weight loss by reducing energy intake in morbidly obese mice and in mice on high-calorie diet. Prieurianin is also anti-adipogenic by inhibiting the proliferation and differentiation of preadipocytes into adipocytes, and induces either dedifferentiation or delipidation of mature adipocytes. Gene expression profiling shows that prieurianin suppresses the expression of genes involved in fat metabolism, and increases the expression of a transcription repressor, zinc finger protein 68 (Zfp68), which inhibits CCAAT/enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated receptor γ (PPARγ), master transcriptional regulators of adipogenesis. The effects of prieurianin are reminiscent of several cytokines that regulate appetite and adipogenesis, and holds promise as an effective anti-obesity drug. Keywords: Time course, prieurianin, obesity, differentiation, adipogenesis, preadipocytes, adipocytes, Zfp68 L1 Cells were treated either with 0.5% DMSO or 2 µM of prieurianin for the following times: 0, 0.25, 0.5,1, 2, 3, 5, 9, 12, 15, 24, 36, 48, 96, 144, 192, 240, and 288 hrs, and then total RNA was purified at the indicated times using the RNeasy Mini kit according to the manufacturer’s instructions. Samples were labeled and hybridized to the Mouse OneArray (Phalanx Biotech Group, Palo Alto, CA) and analyzed for gene expression changes, compared to untreated control undergoing normal differentiation.
2010-02-07 | E-GEOD-15018 | biostudies-arrayexpress
Project description:tRNA-derived fragments (tRFs) are a novel class of non-coding RNA that play an vital role in regulating gene expression at post-transcriptional level. To date, it is completely unknown the regulatory mechanism of tRFs governing fat deposition and adipogenesis. In this study, we used high fat diet successfully induced obese rat model, and used tRFs transcriptome sequencing to select differentially expressed tRFs that response to obesity. We found tRFGluTTC was the highest fold change in the 296 differentially expressed tRFs, which promoted preadipocytes proliferation by increasing the expression of cell cycle regulatory factors. Moreover, tRFGluTTC also suppressed preadipocytes differentiation by reducing lipid accumulation and triglyceride content, and decreasing the expression of genes related to fatty acid synthesis. According to luciferase activity assays, tRFGluTTC directly targeted KLF9, KLF11, and KLF12, and could significantly suppressed the mRNA expression of these target genes. Besides, tRFGluTTC suppressed adipogenesis also accompanied by decreasing the expression of adipogenic transcription factors (AP2, C/EBPα, and PPARγ). Taken together, these results imply that tRFGluTTC may take as a novel epigenetic molecules governing adipogenesis and could be a target for therapeutic intervention in obesity.
2019-04-12 | GSE129685 | GEO
Project description:Abstract Background In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The individual ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to the development of inflammation and detrimental metabolic consequences. However, the molecular mechanisms underlying this fine-tuned regulation are far from being understood. Methods We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low responders (LowR HFD), showed a low susceptibility to the onset of adipose tissue inflammation, as opposed to their HFD counterpart. We identified the discriminants between LowR HFD and HFD vWAT samples and explored their function in Adipose Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. Results We quantified 6051 proteins. Among the candidates that most differentiate LowR HFD from HFD vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in LowR HFD, as compared to HFD. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was totally unknown, was another top-scored hit. SMYD3 expression was significantly higher in LowR HFD vWAT, as confirmed by western blot analysis. In vitro, we found that SMYD3 mRNA and protein levels decrease rapidly along the differentiation process of AD-hMSCs. Moreover, SMYD3 knock-down at the beginning of adipocyte differentiation resulted in reduced cell proliferation and, at longer term, reduced lipid accumulation in adipocytes. Conclusions Our study describes for the first time the role of SMYD3 as a regulator of adipocyte proliferation during the early steps of adipogenesis.
2024-01-03 | PXD043165 | Pride
Project description:MED20 is a non-essential subunit of the transcriptional coactivator Mediator complex, but its physiological function remains largely unknown. Here we show that MED20 plays a key role in the development of adipose tissue and diet-induced obesity. Through affinity purification and candidate screening, we demonstrate that MED20 is targeted for degradation by the anti-obesity CRL4-WDTC1 E3 complex. Depleting MED20 in either 3T3-L1 cells or primary preadipocytes inhibits adipogenesis. Mice with MED20 knocked out in preadipocytes show dramatic defect in the development of brown adipose tissue. Furthermore, removing one allele of Med20 in preadipocytes protects mice from diet-induced obesity, and reverses weight gain in Cul4a- or Cul4b-depleted mice. Mechanistically, MED20 plays a key role in organizing the early adipogenic complex by bridging C/EBPβ and RNA polymerase II and thereby stimulating the transcription of PPARγ. Our study has thus identified MED20 as a potential target for obesity treatment.
2023-12-15 | GSE163281 | GEO
Project description:Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue. Experiment Overall Design: Comparisons of white and brown pre- and mature-adiposytes
2009-04-08 | E-GEOD-7032 | biostudies-arrayexpress
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 µM BPA or 1 µM dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways.
2014-04-15 | GSE56085 | GEO
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 M-BM-5M BPA or 1 M-BM-5M dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways. The study used 40 samples in total which included 5 replicates (cells from 5 unique donors) of 8 different treatments. The 8 treatments were as follows: 1) untreated (negative) control for 48 hours, 2) 25 uM BPA treated for 48 hours, 3) 50 uM BPA treated for 48 hours, 4) untreated (negative) control + insulin for 48 hours, 5) 25 uM BPA + insulin treated for 48 hours, 6) 50 uM BPA + insulin treated for 48 hours, 7) 1uM Dexamethasone + insulin treated for 48 hours, 8) 1uM Dexamethasone + insulin treated for 96 hours.
2014-04-15 | E-GEOD-56085 | biostudies-arrayexpress
Project description:Human antigen R (HuR) protein, a RNA binding protein (RBP), has been reported to regulate essential steps in RNA metabolism and immune response in a variety of cell types, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in all three major adipose tissues including epidydimal, inguinal white and brown adipose tissue, accompanied with systemic glucose intolerance and insulin resistance. Conversely, transgenic overexpression of HuR in adipose tissue prevents the HFD induced obesity by repressing adipogenesis. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts, including the mRNA of Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as a novel posttranscriptional regulator of adipogenesis and provides a new insight into how RNA processing contributes to adipocyte development.
2019-09-09 | GSE124279 | GEO
Project description:Human antigen R (HuR) protein, a RNA binding protein (RBP), has been reported to regulate essential steps in RNA metabolism and immune response in a variety of cell types, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in all three major adipose tissues including epidydimal, inguinal white and brown adipose tissue, accompanied with systemic glucose intolerance and insulin resistance. Conversely, transgenic overexpression of HuR in adipose tissue prevents the HFD induced obesity by repressing adipogenesis. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts, including the mRNA of Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as a novel posttranscriptional regulator of adipogenesis and provides a new insight into how RNA processing contributes to adipocyte development.
2019-09-09 | GSE124278 | GEO