scholarly journals Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells

2020 ◽  
Vol 21 (17) ◽  
pp. 6300
Author(s):  
Yurong Zhao ◽  
Shulin Tang ◽  
Ruqin Lin ◽  
Ting Zheng ◽  
Danyang Li ◽  
...  
Keyword(s):  
Cell Model ◽  
Toxic Effects ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Trichothecene Mycotoxin ◽  
Peroxisome Proliferator Activated Receptor ◽  
Histone 3 ◽  
Toxicological Mechanism ◽  
Late Stages ◽  
Adipogenic Marker

Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.

scholarly journals Anxa2 gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway

2019 ◽  
Vol 316 (2) ◽  
pp. C223-C234 ◽  
Author(s):  
Yong Wang ◽  
Yun-Sheng Cheng ◽  
Xiao-Qiang Yin ◽  
Gang Yu ◽  
Ben-Li Jia
Keyword(s):  
Insulin Resistance ◽  
Gene Silencing ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Global Scale ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Insulin resistance (IR) continues to pose a major threat to public health due to its role in the pathogenesis of metabolic syndrome and its ever-increasing prevalence on a global scale. The aim of the current study was to investigate the efficacy of Anxa2 in obesity-induced IR through the mediation of the NF-κB signaling pathway. Microarray analysis was performed to screen differentially expressed genes associated with obesity. To verify whether Anxa2 was differentially expressed in IR triggered by obesity, IR mouse models were established in connection with a high-fat diet (HFD). In the mouse IR model, the role of differentially expressed Anxa2 in glycometabolism and IR was subsequently detected. To investigate the effect of Anxa2 on IR and its correlation with inflammation, a palmitic acid (PA)-induced IR cell model was established, with the relationship between Anxa2 and the NF-κB signaling pathway investigated accordingly. Anxa2 was determined to be highly expressed in IR. Silencing Anxa2 was shown to inhibit IR triggered by obesity. When Anxa2 was knocked down, elevated expression of phosphorylated insulin receptor substrate 1 (IRS1), IRS1 and peroxisome proliferator-activated receptor coactivator-1a, and glucose tolerance and insulin sensitivity along with 2-deoxy-d-glucose uptake was detected, whereas decreased expression of suppressor of cytokine signaling 3, IL-6, IL-1β, TNF-α, and p50 was observed. Taken together, the current study ultimately demonstrated that Anxa2 may be a novel drug strategy for IR disruption, indicating that Anxa2 gene silencing is capable of alleviating PA or HFD-induced IR and inflammation through its negative regulatory role in the process of p50 nuclear translocation of the NF-κB signaling pathway.

scholarly journals The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2433
Author(s):  
Cécilia Colson ◽  
Pierre-Louis Batrow ◽  
Nadine Gautier ◽  
Nathalie Rochet ◽  
Gérard Ailhaud ◽  
...  
Keyword(s):  
Bioactive Compound ◽  
Antagonistic Effect ◽  
Carnosic Acid ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocyte ◽  
White Adipocytes ◽  
And Function

Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response.

scholarly journals CREB Activation Induces Adipogenesis in 3T3-L1 Cells

2000 ◽  
Vol 20 (3) ◽  
pp. 1008-1020 ◽  
Author(s):  
Jane E. B. Reusch ◽  
Lilliester A. Colton ◽  
Dwight J. Klemm
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Fat Composition ◽  
Specific Factors ◽  
Necessary And Sufficient ◽  
Physiological And Biochemical

ABSTRACT Obesity is the result of numerous, interacting behavioral, physiological, and biochemical factors. One increasingly important factor is the generation of additional fat cells, or adipocytes, in response to excess feeding and/or large increases in body fat composition. The generation of new adipocytes is controlled by several “adipocyte-specific” transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adipocyte-specific factors are expressed only following the induction of adipogenesis. The transcription factor(s) that are involved in initiating adipocyte differentiation have not been identified. Here we demonstrate that the transcription factor, CREB, is constitutively expressed in preadipocytes and throughout the differentiation process and that CREB is stimulated by conventional differentiation-inducing agents such as insulin, dexamethasone, and dibutyryl cAMP. Stably transfected 3T3-L1 preadipocytes were generated in which we could induce the expression of either a constitutively active CREB (VP16-CREB) or a dominant-negative CREB (KCREB). Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by triacylglycerol storage, cell morphology, and the expression of two adipocyte marker genes, peroxisome proliferator activated receptor gamma 2, and fatty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents. These data indicate that activation of CREB was necessary and sufficient to induce adipogenesis. Finally, CREB was shown to bind to putative CRE sequences in the promoters of several adipocyte-specific genes. These data firmly establish CREB as a primary regulator of adipogenesis and suggest that CREB may play similar roles in other cells and tissues.

scholarly journals A meta-analysis study of gene expression datasets in mouse liver under PPARα knockout

2013 ◽  
Vol 95 (2-3) ◽  
pp. 78-88 ◽  
Author(s):  
KAN HE ◽  
ZHEN WANG ◽  
QISHAN WANG ◽  
YUCHUN PAN
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Hepatic Tissue ◽  
Marker Genes ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Microarray Datasets

SummaryGene expression profiling of peroxisome-proliferator-activated receptor α (PPARα) has been used in several studies, but there were no consistent results on gene expression patterns involved in PPARα activation in genome-wide due to different sample sizes or platforms. Here, we employed two published microarray datasets both PPARα dependent in mouse liver and applied meta-analysis on them to increase the power of the identification of differentially expressed genes and significantly enriched pathways. As a result, we have improved the concordance in identifying many biological mechanisms involved in PPARα activation. We suggest that our analysis not only leads to more identified genes by combining datasets from different resources together, but also provides some novel hepatic tissue-specific marker genes related to PPARα according to our re-analysis.

scholarly journals Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates

2006 ◽  
Vol 20 (9) ◽  
pp. 2141-2155 ◽  
Author(s):  
Felix Grün ◽  
Hajime Watanabe ◽  
Zamaneh Zamanian ◽  
Lauren Maeda ◽  
Kayo Arima ◽  
...  
Keyword(s):  
Steroid Receptors ◽  
Cell Model ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Affinity Ligand ◽  
Tributyltin Chloride ◽  
Environmental Agents ◽  
Adipose Mass

Abstract Dietary and xenobiotic compounds can disrupt endocrine signaling, particularly of steroid receptors and sexual differentiation. Evidence is also mounting that implicates environmental agents in the growing epidemic of obesity. Despite a long-standing interest in such compounds, their identity has remained elusive. Here we show that the persistent and ubiquitous environmental contaminant, tributyltin chloride (TBT), induces the differentiation of adipocytes in vitro and increases adipose mass in vivo. TBT is a dual, nanomolar affinity ligand for both the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor γ (PPARγ). TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumulation in adipose depots, liver, and testis of neonate mice and results in increased epididymal adipose mass in adults. In the amphibian Xenopus laevis, ectopic adipocytes form in and around gonadal tissues after organotin, RXR, or PPARγ ligand exposure. TBT represents, to our knowledge, the first example of an environmental endocrine disrupter that promotes adipogenesis through RXR and PPARγ activation. Developmental or chronic lifetime exposure to organotins may therefore act as a chemical stressor for obesity and related disorders.

scholarly journals The endocrine disruptor mono-(2-ethylhexyl)phthalate promotes adipocyte differentiation and induces obesity in mice

2012 ◽  
Vol 32 (6) ◽  
pp. 619-629 ◽  
Author(s):  
Chanjuan Hao ◽  
Xuejia Cheng ◽  
Hongfei Xia ◽  
Xu Ma
Keyword(s):  
Target Genes ◽  
Adipocyte Differentiation ◽  
Cell Model ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Ethylhexyl Phthalate

The environmental obesogen hypothesis proposes that exposure to endocrine disruptors during developmental ‘window’ contributes to adipogenesis and the development of obesity. MEHP [mono-(2-ethylhexyl) phthalate], a metabolite of the widespread plasticizer DEHP [di-(2-ethylhexyl) phthalate], has been found in exposed organisms and identified as a selective PPARγ (peroxisome-proliferator-activated receptor γ) modulator. However, implication of MEHP on adipose tissue development has been poorly investigated. In the present study, we show the dose-dependent effects of MEHP on adipocyte differentiation and GPDH (glycerol-3-phosphate dehydrogenase) activity in the murine 3T3-L1 cell model. MEHP induced the expression of PPARγ as well as its target genes required for adipogenesis in vitro. Moreover, MEHP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to a low dose of MEHP significantly increased b.w. (body weight) and fat pad weight in male offspring at PND (postnatal day) 60. In addition, serum cholesterol, TAG (triacylglycerol) and glucose levels were also significantly elevated. These results suggest that perinatal exposure to MEHP may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders.

scholarly journals Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Sicheng Liu ◽  
Yaguang Zhang ◽  
Su Zhang ◽  
Lei Qiu ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Expression Profiles ◽  
Interaction Network ◽  
Rank Aggregation ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Hub Genes ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Biomarkers

Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.

scholarly journals Toxic Effects of Fumonisin in Mouse Liver Are Independent of the Peroxisome Proliferator-Activated Receptor α

2005 ◽  
Vol 89 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Kenneth A. Voss ◽  
Jie Liu ◽  
Steven P. Anderson ◽  
Corrie Dunn ◽  
J. David Miller ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Toxic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Peroxisome proliferator–activated receptor γ (PPARγ) induces the gene expression of integrin αVβ5 to promote macrophage M2 polarization

2018 ◽  
Vol 293 (43) ◽  
pp. 16572-16582 ◽  
Author(s):  
Qinyu Yao ◽  
Jia Liu ◽  
Zihui Zhang ◽  
Fan Li ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Foam Cell ◽  
Human Peripheral Blood ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Blood Monocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
M2 Polarization

Peroxisome proliferator–activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily and polarizes the macrophages into an anti-inflammatory M2 state. Integrins are transmembrane receptors that drive various cellular functions, including monocyte adhesion and foam cell formation. In this study, we first reported that the expression of integrins αV and β5 was up-regulated by PPARγ activation in RAW264.7 cells and human peripheral blood monocytes. Luciferase reporter and ChIP assay revealed that PPARγ directly bound to the potential PPAR-responsive elements sites in the 5′-flanking regions of both murine and human integrin αV and β5 genes, respectively. In addition, we showed that PPARγ augmented the ligation of integrins αV and β5. Knockdown of integrin αVβ5 by siRNA strategy or treatment with cilengitide, a potent inhibitor of integrin αVβ5, attenuated PPARγ-induced expression of Ym1 (chitinase-like protein 3), Arg1 (Arginase1), Fizz1 (resistin-like molecule RELMα), and other M2 marker genes, suggesting that the heterodimers of integrin αVβ5 were involved in PPARγ-induced M2 polarization. In conclusion, these results provided novel evidence that PPARγ-mediated gene expression and the ensuing ligation of integrins αV and β5 are implicated in macrophage M2 polarization.

scholarly journals PPAR-γRegulates Trophoblast Differentiation in the BeWo Cell Model

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Khrystyna Levytska ◽  
Sascha Drewlo ◽  
Dora Baczyk ◽  
John Kingdom
Keyword(s):  
Cell Proliferation ◽  
Pregnancy Complications ◽  
Cell Model ◽  
Treatment Options ◽  
Bewo Cell ◽  
Peroxisome Proliferator ◽  
Trophoblast Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Baseline Activity

Common pregnancy complications, such as severe preeclampsia and intrauterine growth restriction, disrupt pregnancy progression and impair maternal and fetal wellbeing. Placentas from such pregnancies exhibit lesions principally within the syncytiotrophoblast (SCT), a layer in direct contact with maternal blood. In humans and mice, glial cell missing-1 (GCM-1) promotes differentiation of underlying cytotrophoblast cells into the outer SCT layer. GCM-1 may be regulated by the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ); in mice, PPAR-γpromotes labyrinthine trophoblast differentiation via Gcm-1, and, as we previously demonstrated, PPAR-γactivation ameliorates disease features in rat model of preeclampsia. Here, we aimed to characterize the baseline activity of PPAR-γin the human choriocarcinoma BeWo cell line that mimics SCT formationin vitroand modulate PPAR-γactivity to study its effects on cell proliferation versus differentiation. We report a novel negative autoregulatory mechanism between PPAR-γactivity and expression and show that blocking PPAR-γactivity induces cell proliferation at the expense of differentiation, while these remain unaltered following treatment with the agonist rosiglitazone. Gaining a deeper understanding of the role and activity of PPAR-γin placental physiology will offer new avenues for the development of secondary prevention and/or treatment options for placentally-mediated pregnancy complications.

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