scholarly journals Effects of Thymoquinone on Adipocyte Differentiation in Human Adipose-Derived Stem Cells

2021 ◽  
Author(s):  
Monireh Shahbodi ◽  
Seyed Ahmad Emami ◽  
Behjat Javadi ◽  
Zahra Tayarani-Najaran
Keyword(s):  
Stem Cells ◽  
Cell Viability ◽  
Adipocyte Differentiation ◽  
Flow Cytometric Analysis ◽  
Fatty Acid Synthetase ◽  
Human Adipose Tissue ◽  
Staining Technique ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference

Abstract Background: Obesity is one of the most important public health problems worldwide. Stem cells are primary cells capable of differentiating into different types of cells, and can be used to treat various diseases. Thymoquinone (TQ) has antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. Herein, we aim to investigate the effect of TQ on the process of lipid differentiation in human adipose tissue-derived stem cells (ADSCs). Methods and Results: Quantification of cell surface markers was used by Flow-Cytometry and then, the effect of TQ on cell viability was assessed using alamarBlue test. ADSCs were then subjected to induction of differentiation in the presence of non-cytotoxic concentrations of TQ (6.25, 12.5 and 25 μg/mL). ADSCs differentiation was assessed using Oil-Red staining technique. Moreover, expression of PPARγ (Peroxisome proliferator activated receptor γ) and FAS (Fatty Acid Synthetase) proteins was evaluated using Western blotting analysis. Flow-cytometric analysis demonstrated the expression of CD44 and CD90 markers as mesenchymal stem cells markers on the surface of ADSCs. At concentrations≤100 μg/mL of TQ, no significant difference in cell viability of ADSCs was observed compared to the control. Adipocyte differentiation process significantly decreased at 25 μg/mL (P<0.001) and 12.5 μg/mL (P<0.01) of TQ. The results of the qualitative examination of Lipid Droplets also confirmed these results. Western-blot analysis showed that TQ at 12.5 (p<0.05) and 25 μg/mL (p<0.01) reduced FAS/β-actin ratio compared to the positive group.Conclusions: This study showed that TQ can reduce the process of differentiation of fat stem cells into fat cells and might be considered as an anti-obesity compound.

scholarly journals Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes

2016 ◽  
Vol 242 (10) ◽  
pp. 1079-1085 ◽  
Author(s):  
Ignazio Barbagallo ◽  
Giovanni Li Volti ◽  
Fabio Galvano ◽  
Guido Tettamanti ◽  
Francesca R Pluchinotta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
In Vitro Study ◽  
Human Adipose Tissue ◽  
Sirtuin 1 ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1β were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our in vitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue. Impact statement In the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

2013 ◽  
Vol 304 (11) ◽  
pp. C1091-C1097 ◽  
Author(s):  
Takeshi Honda ◽  
Aiko Ishii ◽  
Makoto Inui
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Pparγ Expression

PDZRN3, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancer-binding protein (C/EBP)-β during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-γ (PPARγ), an upstream regulator of aP2 and C/EBPα, at both the mRNA and protein levels. Among transcription factors that control the expression of PPARγ, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBPβ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBPβ and consequent suppression of PPARγ expression.

scholarly journals Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Xingming Shi ◽  
Mark Hamrick ◽  
Carlos M. Isales
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Energy Balance ◽  
Therapeutic Strategy ◽  
Adipocyte Differentiation ◽  
Bone Development ◽  
Nuclear Hormone Receptor ◽  
Liver Fat ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator-activated receptor gamma (PPAR-γ) belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP), fat (e.g., leptin), muscle (e.g., myostatin), or bone (e.g., GILZ) can in turn modulate PPAR expression and/or function. Of the two PPAR-γisoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation.

scholarly journals PPAR-γSignaling Crosstalk in Mesenchymal Stem Cells

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ichiro Takada ◽  
Alexander P. Kouzmenko ◽  
Shigeaki Kato
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Protein Complexes ◽  
Regulatory Function ◽  
Target Cells ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γacts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β) had been known to inhibit adipocyte differentiation in mesenchymal stem cells (MSCs), we examined the effect of these cytokines on the transactivation function of PPAR-γ. We found that the TNF-α/IL-1-activated TAK1/TAB1/NIK (NFκB-inducible kinase) signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR-γby blocking the receptor binding to the cognate DNA response elements. Furthermore, it has been shown that the noncanonical Wnts are expressed in MSCs and that Wnt-5a was capable to inhibit transactivation by PPAR-γ. Treatment with Wnt5a-activated NLK (nemo-like kinase) induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1) protein complexes with PPAR-γ. This resulted in histoneH3K9 tri-methylation at PPAR-γtarget gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR-γregulatory function in its target cells and tissues.

scholarly journals Sulforaphene Suppresses Adipocyte Differentiation via Induction of Post-Translational Degradation of CCAAT/Enhancer Binding Protein Beta (C/EBPβ)

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 758
Author(s):  
Hee Yang ◽  
Min Jeong Kang ◽  
Gihyun Hur ◽  
Tae Kyung Lee ◽  
In Sil Park ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Early Stage ◽  
Binding Protein ◽  
Human Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Molecular Mechanism Of Action ◽  
The Stability

Adipocyte differentiation (adipogenesis) is a crucial process that determines the total number and size of mature adipocytes that will develop. In this study, the anti-adipogenic effect of sulforaphene (SFEN), a dietary isothiocyanate (ITC) derived from radish, is investigated both in 3T3-L1 pre-adipocytes and in human adipose tissue-derived stem cells. The results revealed that SFEN significantly inhibit adipogenic cocktail-induced adipocyte differentiation and lipid accumulation at the early stage of adipogenesis. Additionally, the effects are more potent compared to those of other ITCs derived from various cruciferous vegetables. As a related molecular mechanism of action, SFEN promotes the post-translational degradation of CCAAT/enhancer-binding protein (C/EBP) β by decreasing the stability of C/EBPβ, which is responsible for decreasing the expression of master regulatory proteins such as peroxisome proliferator-activated receptor γ and C/EBPα. Collectively, these results suggest that the intake of SFEN-enriched natural materials could be helpful as a strategy for preventing obesity.

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

2003 ◽  
Vol 375 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Lise MADSEN ◽  
Rasmus K. PETERSEN ◽  
Morten B. SØRENSEN ◽  
Claus JØRGENSEN ◽  
Philip HALLENBORG ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Critical Evaluation ◽  
Nordihydroguaiaretic Acid ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARγ (peroxisome proliferator-activated receptor γ) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARγ ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARγ ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3–4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARγ ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

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