scholarly journals Piceatannol Is Superior to Resveratrol at Suppressing Adipogenesis in Human Visceral Adipose-Derived Stem Cells

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 366
Author(s):  
In Sil Park ◽  
Youngjin Han ◽  
HyunA Jo ◽  
Ki Won Lee ◽  
Yong Sang Song
Keyword(s):  
Stem Cells ◽  
Metabolic Diseases ◽  
Binding Protein ◽  
Visceral Obesity ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Fatty Acid Binding ◽  
Chemical Structures ◽  
Visceral Adipose ◽  
Adipogenic Effect

Resveratrol (3,4′,5-trans-trihydroxystilbene) and piceatannol (3,3′,4′,5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 μM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 μM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 μM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.

scholarly journals Characterization and comparative DNA methylation profiling of four adipogenic genes in adipose-derived stem cells and dedifferentiated fat cells from aging subjects

Human Cell ◽  
2020 ◽  
Vol 33 (4) ◽  
pp. 974-989
Author(s):  
Kallapat Tansriratanawong ◽  
Isao Tabei ◽  
Hiroshi Ishikawa ◽  
Akihiro Ohyama ◽  
Junko Toyomura ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Binding Protein ◽  
Dependent Manner ◽  
Adipose Derived Stem Cells ◽  
Multilineage Differentiation ◽  
Fatty Acid Binding ◽  
Dna Methylation Profiling ◽  
Dfat Cells ◽  
Methylation Profiling

Abstract Adipose-derived stem cells (ASCs) and dedifferentiated fat (DFAT) cells are alternative cell sources in tissue engineering and regeneration because they are easily obtained and exhibit multilineage differentiation. However, aging may attenuate their regenerative potential and metabolic functions. Reports characterizing DFAT cells derived from aging donors are rare, and comparisons of DNA methylation profiles between aging ASCs and DFAT cells are poorly understood. Therefore, this study aimed to characterize DFAT cells relative to ASCs derived from aging subjects and compare the DNA methylation profiles of four adipogenic genes in these cells. ASCs and DFAT cells from aging donors exhibited characteristics similar to those of stem cells, including colony formation, proliferation, and multilineage differentiation abilities. However, compared with ASCs, DFAT cells exhibited increased proliferation, smooth muscle actin alpha (SMA-α) expression and decreased cellular senescence. DNA methylation profiling of ASCs and DFAT cells by combined bisulfite restriction analysis (COBRA) demonstrated hypermethylation patterns in three potent adipogenic genes—peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 4 (FABP4), and lipoprotein lipase (LPL)—but hypomethylation of CCAAT/enhancer binding protein alpha (C/EBPα) in the aging group. Statistically significant differences were observed between the aging group and the young group. Epigenetic regulation maintains the stability of ASCs and DFAT cells in an age-dependent manner. Our findings suggested that although the DNA methylation patterns of three adipogenic genes correlated with hypermethylation and aging, ASCs and DFAT cells exhibited cellular stability and several stem cell characteristics, offering further opportunities for personalized regeneration and energy maintenance by adipogenesis during aging.

scholarly journals CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Smarajit Chakraborty ◽  
Wee Kiat Ong ◽  
Winifred W. Y. Yau ◽  
Zhihong Zhou ◽  
K. N. Bhanu Prakash ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Human Subject ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Target Cells ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Direct Role ◽  
Differentiation Potential

Abstract Background Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation. Methods We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library. Results We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC’s adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening. Conclusion Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.

scholarly journals Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes

2010 ◽  
Vol 24 (3) ◽  
pp. 526-539 ◽  
Author(s):  
Séverine Kirchner ◽  
Tiffany Kieu ◽  
Connie Chow ◽  
Stephanie Casey ◽  
Bruce Blumberg
Keyword(s):  
Stem Cells ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
In Utero ◽  
Gene Marker ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Stromal Stem Cells ◽  
Adipose Mass

Abstract The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARγ activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARγ antagonists, suggesting that activation of PPARγ mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARγ target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time.

scholarly journals Traditional Herbal Formula Oyaksungi-San Inhibits Adipogenesis in 3T3-L1 Adipocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Chang-Seob Seo ◽  
Hyeun-Kyoo Shin ◽  
Soo-Jin Jeong
Keyword(s):  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Herbal Formula ◽  
Related Factors ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Gpdh Activity ◽  
Protein Levels ◽  
Intracellular Lipid Accumulation ◽  
Glycerol 3 Phosphate Dehydrogenase

Background. Oyaksungi-san (OYSGS) is a herbal formula that has been used for treating cardiovascular diseases in traditional Asian medicine. Here, we investigated the antiadipogenic effect of OYSGS extract in 3T3-L1 adipose cells.Methods. 3T3-L1 preadipocytes were differentiated into adipocytes with or without OYSGS. After differentiation, we measured Oil Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity, leptin production, mRNA, and protein levels of adipogenesis-related factors.Results. OYSGS extract dramatically inhibited intracellular lipid accumulation in the differentiated adipocytes. It also significantly suppressed the (GPDH) activity, triglyceride (TG) content, and leptin production by reducing the expression of adipogenesis-related genes including lipoprotein lipase, fatty acid binding protein 4, CCAAT/enhancer-binding protein-alpha (C/EBP-α), and peroxisome proliferator-activated receptor gamma (PPAR-γ). Furthermore, OYSGS clearly enhanced phosphorylation of AMP-activated protein kinase (AMPK) as well as its substrate acetyl CoA (ACC) carboxylase.Conclusions. Our results demonstrate that OYSGS negatively controls TG accumulation in 3T3-L1 adipocytes. We suggest antiadipogenic activity of OYSGS and its potential benefit in preventing obesity.

Thermosensitive and Cell-Adhesive Pluronic Hydrogels for Human Adipose-Derived Stem Cells

2007 ◽  
Vol 342-343 ◽  
pp. 301-304 ◽  
Author(s):  
Kwi Deok Park ◽  
Hong Hee Jung ◽  
Jun Sik Son ◽  
Jong Won Rhie ◽  
Ki Dong Park ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Pluronic F127 ◽  
Peptide Ligand ◽  
Temperature Sensitive ◽  
Adipose Derived Stem Cells ◽  
Chemical Structures ◽  
Injectable Scaffold ◽  
Cell Adhesive ◽  
Critical Micelle Temperature

Pluronic F127 has received increasing attention over many years as drug delivery systems, biomaterials, and hydrogels for tissue engineering. In this study, we synthesized temperature-sensitive and cell-adhesive triblock F127 copolymers, in which Arg-Gly-Asp (RGD) peptide ligand was grafted to Pluronic F127-4-methacryloxyethyl trimellitic anhydride (4-META) to obtain F127-META-RGD. The chemical structures of the F127-META-RGD block copolymers were confirmed by FTIR, 1H and 13C NMR, and GPC. The resultant F127-META-RGD showed very similar thermosensitive behaviors to F127 and F127-META. The critical micelle temperature (CMT) of the F127 copolymers decreased in the order of F127 < F127-META < F127-META-RGD, whereas the particle size followed an opposite trend. Interactions between the F127 copolymers and adipose-derived stem cells (ASC) were evaluated in terms of cell adhesion and proliferation on the hydrogel. These thermosensitive RGD-grafted Pluronic hydrogels that display the enhanced cell adhesiveness, are expected to be useful as a functional injectable scaffold for tissue engineering.

scholarly journals Enhanced Therapeutic Potential of the Secretome Released from Adipose-Derived Stem Cells by PGC-1α-Driven Upregulation of Mitochondrial Proliferation

2019 ◽  
Vol 20 (22) ◽  
pp. 5589
Author(s):  
Jaeim Lee ◽  
Ok-Hee Kim ◽  
Sang Chul Lee ◽  
Kee-Hwan Kim ◽  
Jin Sun Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Tissue Expression ◽  
In Vitro Models ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

mRNA expression of genes related to fat deposition during in vitro ovine adipogenesis

2019 ◽  
Vol 99 (4) ◽  
pp. 764-771 ◽  
Author(s):  
Baojun Li ◽  
Liying Qiao ◽  
Xiaoru Yan ◽  
Tao Shi ◽  
Duanyang Ren ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Binding Protein ◽  
Adipogenic Differentiation ◽  
Fat Deposition ◽  
Peroxisome Proliferator ◽  
Induced Differentiation ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Ppar Γ

Fat deposition in animals involves adipogenic differentiation guided by transcriptional factors and other key factors. To understand the molecular mechanism underlying ovine adipogenic differentiation, the dynamic mRNA expression of key genes related to fat deposition, including peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid-binding protein 4 (FABP4), FABP5, and cellular retinoic acid-binding protein 2 (CRABP2), were analyzed during in vitro differentiation of ovine preadipocytes. The stromal vascular cells from underneath the tail fat tissue of 1-wk-old sheep were isolated and cultured, and the preadipocytes were induced using a cocktail of 3-isobutyl-1-methylxanthine, insulin, dexamethasone, and troglitazone. The cultivated cells were collected at different time points after induced differentiation. The expression levels of PPAR-γ, FABP4, FABP5, and CRABP2 were studied by quantitative real-time polymerase chain reaction. The expressions of these genes in sheep were compared with those in human and mouse retrieved from the Gene Expression Omnibus DataSets. We observed that the expression of PPAR-γ, FABP4, and FABP5 was increased upon differentiation of ovine preadipocytes, as in humans and mice. The expression of CRABP2 was sharply increased from days 0 to 2 after induced differentiation and was subsequently decreased. This expression pattern of CRABP2 was different from that observed in humans and mice. Our results provide new insights into the function of these genes in fat deposition.

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