scholarly journals Tributyltin induces a transcriptional response without a brite adipocyte signature in adipocyte models

2018 ◽  
Author(s):  
Stephanie Kim ◽  
Amy Li ◽  
Stefano Monti ◽  
Jennifer J. Schlezinger
Keyword(s):  
Gene Expression ◽  
Mitochondrial Biogenesis ◽  
Adipocyte Differentiation ◽  
Metabolic Effects ◽  
Pathway Enrichment Analysis ◽  
Peroxisome Proliferator ◽  
Multipotent Mesenchymal Stromal Cell ◽  
Data Set ◽  
Peroxisome Proliferator Activated Receptor ◽  
L1 Data

AbstractTributyltin (TBT), a peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR) ligand and founding member of the environmental obesogen chemical class, induces adipocyte differentiation and suppresses bone formation. A growing number of environmental PPARγ ligands are being identified. However, the potential for environmental PPARγ ligands to induce adverse metabolic effects has been questioned because PPARγ is a therapeutic target in treatment of type II diabetes. We evaluated the molecular consequences of TBT exposure during bone marrow multipotent mesenchymal stromal cell (BM-MSC) differentiation in comparison to rosiglitazone, a therapeutic PPARγ ligand, and LG100268, a synthetic RXR ligand. Mouse primary BM-MSCs (female, C57BL/6J) undergoing bone differentiation were exposed to maximally efficacious and human relevant concentrations of rosiglitazone (100 nM), LG100268 (100 nM) or TBT (80 nM) for 4 days. Gene expression was assessed using microarrays, and in silico functional annotation was performed using pathway enrichment analysis approaches. Pathways related to osteogenesis were downregulated by all three ligands, while pathways related to adipogenesis were upregulated by rosiglitazone and TBT. However, pathways related to mitochondrial biogenesis and brown-in-white (brite) adipocyte differentiation were more significantly upregulated in rosiglitazone-treated than TBT-treated cells. The lack of induction of genes involved in adipocyte energy dissipation by TBT was confirmed by an independent gene expression analysis in BM-MSCs undergoing adipocyte differentiation and by analysis of a publically available 3T3 L1 data set. Furthermore, rosiglitazone, but not TBT, induced mitochondrial biogenesis. This study is the first to show that an environmental PPARγ ligand has a limited capacity to induce health promoting activities of PPARγ.

scholarly journals Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

2004 ◽  
Vol 24 (8) ◽  
pp. 3430-3444 ◽  
Author(s):  
Jong Bae Seo ◽  
Hyang Mi Moon ◽  
Woo Sik Kim ◽  
Yun Sok Lee ◽  
Hyun Woo Jeong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Gene Promoters ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Gene Expression ◽  
X Receptors

ABSTRACT Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro. In adipocytes, LXR activation with T0901317 primarily enhanced the expression of lipogenic genes such as the ADD1/SREBP1c and FAS genes and substantially increased the expression of the adipocyte-specific genes encoding PPARγ (peroxisome proliferator-activated receptor γ) and aP2. Administration of the LXR agonist T0901317 to lean mice promoted the expression of most lipogenic and adipogenic genes in fat and liver tissues. It is of interest that the PPARγ gene is a novel target gene of LXR, since the PPARγ promoter contains the conserved binding site of LXR and was transactivated by the expression of LXRα. Moreover, activated LXRα exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPARγ, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXRα by small interfering RNA attenuated adipocyte differentiation. Taken together, these results suggest that LXR plays a role in the execution of adipocyte differentiation by regulation of lipogenesis and adipocyte-specific gene expression.

scholarly journals The Metabolic Effects of Traditional Chinese Medication Qiliqiangxin on H9C2 Cardiomyocytes

2015 ◽  
Vol 37 (6) ◽  
pp. 2246-2256 ◽  
Author(s):  
Shenghui Lin ◽  
Xiaoting Wu ◽  
Lichan Tao ◽  
Yihua Bei ◽  
Haifeng Zhang ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Oxidative Metabolism ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Duration Of Treatment ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor

Background/Aims: A traditional Chinese medicine, Qiliqiangxin (QLQX) has been identified to perform protective effects on myocardium energy metabolism in mice with acute myocardial infarction, though the effects of QLQX on myocardial mitochondrial biogenesis under physiological condition is still largely elusive. Methods: H9C2 cells were treated with different concentrations of QLQX (0.25, 0.5, and 1.0 µg/mL) from 6 to 48 hours. Oxidative metabolism and glycolysis were measured by oxygen consumption and extracellular acidification with XF96 analyzer (SeaHorse). Mitochondrial content and ultrastructure were assessed by Mitotracker staining, confocal microscopy, flow cytometry, and transmission electron microscopy. Mitochondrial biogenesis-related genes were measured by qRT-PCR and Western blot. Results: H9C2 cells treated with QLQX exhibited increased glycolysis at earlier time points (6, 12, and 24 hours), while QLQX could enhance oxidative metabolism and mitochondrial uncoupling in H9C2 cells with longer duration of treatment (48 hours). QLQX also increased mitochondrial content and mitochondrial biogenesis-related gene expression levels, including 16sRNA, SSBP1, TWINKLE, TOP1MT and PLOG, with an activation of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and its downstream effectors. Silencing PGC-1α could abolish the increased mitochondrial content in H9C2 cells treated with QLQX. Conclusion: Our study is the first to document enhanced metabolism in cardiomyocytes treated with QLQX, which is linked to increased mitochondrial content and mitochondrial biogenesis via activation of PGC-1α.

scholarly journals Transcription Suppression of Peroxisome Proliferator-Activated Receptor γ2 Gene Expression by Tumor Necrosis Factor α via an Inhibition of CCAAT/ Enhancer-binding Protein δ during the Early Stage of Adipocyte Differentiation

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4948-4956 ◽  
Author(s):  
Masataka Kudo ◽  
Akira Sugawara ◽  
Akira Uruno ◽  
Kazuhisa Takeuchi ◽  
Sadayoshi Ito
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Gene Transcription ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Enhancer Binding Protein

Abstract TNFα is known to inhibit adipocyte differentiation and induce insulin resistance. Moreover, TNFα is known to down-regulate peroxisome proliferator-activated receptor (PPAR)γ2, an adipocyte-specific nuclear receptor of insulin-sensitizer thiazolidinediones. To clarify molecular mechanisms of TNFα- mediated PPARγ2 down-regulation, we here examined the effect of TNFα on transcription regulation of PPARγ2 gene expression during the early stage of adipocyte differentiation. 3T3-L1 preadipocytes (2 d after 100% confluent) were incubated in a differentiation mixture (dexamethasone, insulin, 3-isobutyl-1-methlxanthine), with or without 50 ng/ml TNFα, for 24 h. TNFα significantly decreased PPARγ2 expression both at mRNA and protein levels (to ∼40%), as well as aP2 mRNA expression. The mouse PPARγ2 gene promoter region (2.2-kb) was isolated and was used for luciferase reporter assays by transient transfection. TNFα significantly suppressed PPARγ2 gene transcription (to ∼50%), and deletion analyses demonstrated that the suppression was mediated via CCAAT/enhancer-binding protein (C/EBP) binding elements at the −320/−340 region of the promoter. Moreover, TNFα significantly decreased expression of C/EBPδ mRNA and protein levels (to ∼40%). EMSA, using 3T3-L1 cells nuclear extracts with the −320/−340 region as a probe, demonstrated the binding of C/EBPδ to the element, which was significantly decreased by TNFα treatment. Overexpression of CEBP/δ prevented the TNFα-mediated suppression of PPARγ2 transactivation. Taken together, TNFα suppresses PPARγ2 gene transcription by the inhibition of C/EBPδ expression and its DNA binding during the early stage of adipocyte differentiation, which may contribute to the inhibition of adipocyte differentiation, as well as the induction of insulin resistance.

Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise

2006 ◽  
Vol 42 ◽  
pp. 13-29 ◽  
Author(s):  
Anna-Maria Joseph ◽  
Henriette Pilegaard ◽  
Anastassia Litvintsev ◽  
Lotte Leick ◽  
David A. Hood
Keyword(s):  
Gene Expression ◽  
Mitochondrial Biogenesis ◽  
Protein Import ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Mitochondrial Fission ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Control Of Gene Expression ◽  
Genes Encoding

Every time a bout of exercise is performed, a change in gene expression occurs within the contracting muscle. Over the course of many repeated bouts of exercise (i.e. training), the cumulative effects of these alterations lead to a change in muscle phenotype. One of the most prominent of these adaptations is an increase in mitochondrial content, which confers a greater resistance to muscle fatigue. This essay reviews current knowledge on the regulation of exercise-induced mitochondrial biogenesis at the molecular level. The major steps involved include, (i) transcriptional regulation of nuclear-encoded genes encoding mitochondrial proteins by the coactivator peroxisome-proliferator-activated receptor g coactivator-1, (ii) control of mitochondrial DNA gene expression by the transcription factor Tfam, (iii) mitochondrial fission and fusion mechanisms, and (iv) import of nuclear-derived gene products into the mitochondrion via the protein import machinery. It is now known that exercise can modify the rates of several of these steps, leading to mitochondrial biogenesis. An understanding of how exercise can produce this effect could help us decide whether exercise is beneficial for patients suffering from mitochondrial disorders, as well as a variety of metabolic diseases.

Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARγ

2010 ◽  
Vol 427 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Francesca Aguiló ◽  
Nuria Camarero ◽  
Joana Relat ◽  
Pedro F. Marrero ◽  
Diego Haro
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Ketone Bodies ◽  
Physiological Role ◽  
Direct Interaction ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Promoter

In the cytosol of lipogenic tissue, ketone bodies are activated by AACS (acetoacetyl-CoA synthetase) and incorporated into cholesterol and fatty acids. AACS gene expression is particularly abundant in white adipose tissue, as it is induced during adipocyte differentiation. In order to elucidate the mechanism controlling the gene expression of human AACS and to clarify its physiological role, we isolated the human promoter, characterized the elements required to initiate transcription and analysed the expression of the gene in response to PPARγ (peroxisome-proliferator-activated receptor γ), an inducer of adipogenesis. We show that the human AACS promoter is a PPARγ target gene and that this nuclear receptor is recruited to the AACS promoter by direct interaction with Sp1 (stimulating protein-1).

scholarly journals EFFECT OF TROGLITAZONE ON MORPHOLOGICAL CHANGES AND PPAR-γ GENE EXPRESSION IN 3T3-L1 ADIPOCYTE CELLS

2019 ◽  
Vol 6 (1) ◽  
pp. 53
Author(s):  
Asri Sulfianti ◽  
Mayriska Triwulansari ◽  
. Nuralih ◽  
. Churiyah
Keyword(s):  
Gene Expression ◽  
Adipocyte Differentiation ◽  
Morphological Changes ◽  
Mrna Level ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoglycemic Agent ◽  
Ppar Γ ◽  
Oil Red O Staining ◽  
Oil Red O

Efek Troglitazone terhadap Perubahan Morfologi dan Ekspresi Gen PPAR- γ di Dalam Sel Adiposa 3T3-L1 ABSTRACT3T3-L1 cells are extensively used as a model to study adipogenesis. However, one major concern is the prolonged period of time it takes the cells to differentiate into adipocytes form. To induce this differentiation, the adipogenic induction media is required. In this study, troglitazone, a hypoglycemic agent was added to adipogenic induction media and observed in order to determine the morphological changes and peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression in 3T3-L1 differentiation. It is generally known that PPAR-ꝩ plays an important role as a transcription factor in adipocyte differentiation. Based on Oil Red O Staining, adipogenic induction with or without troglitazone changed the 3T3-L1 pre-adipocytes into mature round fat cells characterized by red droplet lipids. This cell also had a high absorbance level and degree of droplet accumulation of P≤ 0.05 in each group. In addition, cells treated by troglitazone had the highest PPAR-ꝩ mRNA level (1.9 fold) than those treated by adipogenic induction media without troglitazone or cells un-treated at all. Keywords: 3T3-L1, adipocyte, differentiation, PPAR-ꝩ, troglitazone ABSTRAKSel 3T3-L1 adalah jenis sel yang banyak digunakan dalam studi adipogenesis. Namun, salah satu kelemahan sel tersebut adalah lamanya waktu yang dibutuhkan bagi sel pre-adiposa untuk berdiferensiasi menjadi sel adiposa. Selain itu, dibutuhkan pula media induksi khusus untuk mengubah sel menjadi sel adiposa. Pada penelitian ini, kami mengobservasi fungsi troglitazone, sebagai antidiabetes terhadap perubahan morfologi dan ekspresi gen peroxisome proliferator-activated receptor gamma (PPAR-γ). Telah diketahui bahwa PPAR-ꝩ berperan penting sebagai factor transkripsi dalam diferensasi sel adiposa. Berdasarkan pewarnaan ORO, induksi sel pre-adiposa 3T3-L1 dengan media induksi dengan dan tanpa troglitazone merubah sel preadiposa menjadi sel berbentuk bulat yang dikarakterisasi dengan akumulasi droplet lemak. Nilai absorbansi sel adiposa juga menandakan adanya perbedaan yang signifikan antara kelompok sel yang diberi troglitazone dan tidak, dan sel tanpa diberi media induksi. Sementara, pada kelompok sel yang diberi troglitazone memiliki ekspresi mRNA PPAR-ꝩ (1,9 kali) tertinggi jika dibandingkan dengan sel yang diberi media induksi tanpa troglitazone, dan tanpa media induksi sama sekali.Kata Kunci: 3T3-L1, adiposa, diferensiasi, PPAR-ꝩ, troglitazone

FOOD SECURITY: EFFECT ON PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPARY) AND BMI AMONG YOUNG ADULT

2016 ◽  
Vol 78 (6-8) ◽  
Author(s):  
Nur Atiqah Alias ◽  
Norazmir Md Nor ◽  
Mohd Fahmi Mastuki ◽  
Khairil Anuar Md Isa
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Food Security ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Food Security Status ◽  
Metabolic Indices ◽  
Pparγ Expression ◽  
Sensitivity Increase

Food security status is a method used to differentiate food secure and food insecure experience. Throughout our lives, nutritious food and lifestyle are closely related with most lifestyle-associated illness. This study investigated young adults in both groups to determine molecular changes on gene expression of peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ plays an important role in adipocyte differentiation, fatty acids, and insulin sensitivity. Increase of PPARγ expression help to improve metabolic indices in dysregulated metabolism associated with obesity, diabetes, and cardiovascular disease. There are no significant differences (P>0.05) of PPARγ expression and BMI for both groups. However, expression of PPARγ is detected in earlier amplification for food insecure group. Mean of BMI (20.70± 3.025) is also slightly higher in food insecure group than food secure. Conclusively, there are some effects on expression of PPARγ and BMI based on food security status. 

scholarly journals Serotonin 5-HT2A receptor activity mediates adipocyte differentiation through control of adipogenic gene expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bangning Yu ◽  
Diana M. Battaglia ◽  
Timothy P. Foster ◽  
Charles D. Nichols
Keyword(s):  
Gene Expression ◽  
Adipocyte Differentiation ◽  
Receptor Activity ◽  
Peroxisome Proliferator ◽  
Differentiation Process ◽  
Receptor Antagonists ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peripheral Tissues ◽  
Ppar Γ ◽  
Novel Therapeutic Strategies

AbstractSerotonin 5-HT2 receptors are expressed in many tissues and play important roles in biological processes. Although the 5-HT2A receptor is primarily known for its role in central nervous system, it is also expressed in peripheral tissues. We have found that 5-HT2A receptor antagonists inhibit human subcutaneous primary adipocyte differentiation. We also show that siRNA knockdown of the 5-HT2A receptor blocks differentiation. Using gene expression analysis in combination with receptor antagonists we found that activity of 5-HT2A receptors is necessary very early in the differentiation process to mediate expression of adipogenic genes, including peroxisome proliferator-activated receptor gamma (ppar-γ), adipocyte protein 2 (aP2), adiponectin, and serine/threonine-protein kinase 1 (sgk1). We show here for the first time that 5-HT2A receptor activity is necessary for differentiation of human primary subcutaneous preadipocytes to adipocytes, and that 5-HT2A receptor activity mediates key genes related to adipogenesis during this process. Importantly, this work contributes to a greater understanding of the adipocyte differentiation process, as well as to the role of 5-HT2A receptors in peripheral tissues, and may be relevant to the development of novel therapeutic strategies targeting this receptor for the treatment of obesity related diseases.

scholarly journals Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism

2018 ◽  
Vol 10 (446) ◽  
pp. eaar5987 ◽  
Author(s):  
Xuan Zhang ◽  
Chenyi Xue ◽  
Jennie Lin ◽  
Jane F. Ferguson ◽  
Amber Weiner ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
De Novo ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Data Set ◽  
Peroxisome Proliferator Activated Receptor ◽  
Healthy Humans ◽  
Subcutaneous Adipose

Long intergenic noncoding RNAs (lincRNAs) have emerged as important modulators of cellular functions. Most lincRNAs are not conserved among mammals, raising the fundamental question of whether nonconserved adipose-expressed lincRNAs are functional. To address this, we performed deep RNA sequencing of gluteal subcutaneous adipose tissue from 25 healthy humans. We identified 1001 putative lincRNAs expressed in all samples through de novo reconstruction of noncoding transcriptomes and integration with existing lincRNA annotations. One hundred twenty lincRNAs had adipose-enriched expression, and 54 of these exhibited peroxisome proliferator–activated receptor γ (PPARγ) or CCAAT/enhancer binding protein α (C/EBPα) binding at their loci. Most of these adipose-enriched lincRNAs (~85%) were not conserved in mice, yet on average, they showed degrees of expression and binding of PPARγ and C/EBPα similar to those displayed by conserved lincRNAs. Most adipose lincRNAs differentially expressed (n = 53) in patients after bariatric surgery were nonconserved. The most abundant adipose-enriched lincRNA in our subcutaneous adipose data set, linc-ADAL, was nonconserved, up-regulated in adipose depots of obese individuals, and markedly induced during in vitro human adipocyte differentiation. We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis.

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