scholarly journals Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 13 ◽  
Author(s):  
In Sil Park ◽  
Boyun Kim ◽  
Youngjin Han ◽  
Hee Yang ◽  
Untack Cho ◽  
...  

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 366
Author(s):  
In Sil Park ◽  
Youngjin Han ◽  
HyunA Jo ◽  
Ki Won Lee ◽  
Yong Sang Song

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mingzhu Jin ◽  
Yujing Zhang ◽  
Yuanyuan Bian ◽  
Ruiqun Qi ◽  
Xinghua Gao

Adipose-derived stem cells (ADSCs) are an abundant cell source and provide an easy way to harvest mesenchymal stem cells, which are the focus of considerable attention in regenerative medicine. Electric fields (EF) play roles in many biological events and have been reported to promote cell proliferation, migration, and differentiation. In this study, ADSCs were treated with a direct current electric field (DCEF) of either 0 (control group) or 300 mV/mm (EF group) for six hours. RNA screening and analysis revealed that 66, 164, 26, and 1310 circRNAs, lncRNAs, miRNAs, and mRNAs, respectively, were differentially expressed in the DCEF-treated ADSCs compared with untreated ADSCs. Differentially expressed mRNAs were enriched in the MAPK signaling pathway, TNF signaling pathway, and some other pathways. ANXA1, ERRFI1, JAG1, EPHA2, PRR9, and H2AFY2 were related to the keratinocyte differentiation process. Competing endogenous RNA (ceRNA) networks were constructed on the basis of genes in the MAPK signaling pathway. Twenty-one RNAs in the above networks were randomly chosen, and their expression was validated using qRT-PCR, which showed the same expression trends as the RNA sequencing analysis. The MAPK signaling pathway is of great importance in the ADSC processes that occur in a DCEF, including keratinocyte differentiation. Several ceRNAs may participate in the regulation of MAPK signaling. This study may give new insight into the proliferation, migration, and differentiation of ADSCs, which will be valuable for tissue engineering and regenerative medicine.


2021 ◽  
Author(s):  
Xiaojun Ma ◽  
Yujie Guo ◽  
Pengfei Li ◽  
Jingjing Xu ◽  
Shengqi Dong ◽  
...  

Abstract Background: Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Polyunsaturated fatty acids (PUFAs) are essential in maintaining normal brain function. However, little is known about the impact of dietary n-6/n-3 PUFA ratio on AD-like pathology, especially in high-fat diet (HFD)-fed AD model mice. Methods: In the present study, the APP/PS1 mice were treated with 60% HFD for 3.5 months to induced insulin resistance. After that, 45% HFD with different n-6/n-3 PUFA ratios (n-6/n-3=1:1, 5:1 or 16:1) was applied for additional 3.5 months treatment. Following the dietary intervention, the behavior of mice was observed using the Water maze. Following behavioral testing, the animals were euthanized, and serum and tissue samples were collected for biochemical, histological and pathological analyses and evaluation. Cortical fatty acid profile was measured by gas chromatography. Western Blot and immunohistochemistry methods were used to detect protein expression of molecules related to AD pathology and insulin signaling pathway(s) in the brain sample tissues. Immunofluorescence assay was used to uncover the expression and migration of NF-κB in the cortex. qPCR method was applied to determine the gene expression of cortical pro-inflammatory cytokines.Results: HFD caused insulin resistance, increased serum IL-6 and TNF-α level, elevated cortical soluble Aβ1-40, Aβ1-42 content, and increased brain n-6/n-3 PUFAs ratio in APP/PS1 mice. Increased APP and BACE1 protein expression and p-IR/IR ratio, but decreased pro-inflammatory cytokines mRNA expression was observed in the cortex from 60% HFD-fed APP/PS1 mice. N-3 PUFAs rich diet (n-6/n-3=1:1) relieved insulin resistance and hyperlipidemia induced by 60% HFD. Cortical soluble Aβ1-40 and Aβ1-42 contents, the expression of cortical APP, GLUT3, insulin metabolism related molecules, and NF-κB pathway downstream pro-inflammatory cytokines showed a dietary n-6/n-3 PUFAs ratio-dependent way, indicating that dietary n-6/n-3 PUFA ratio plays a critical role in modifying the responses of serum inflammatory cytokine, AD pathology, cortical n-6/n-3 PUFAs ratio, insulin signaling and neuroinflammation to HFD treatment.Conclusion: Dietary n-6/n-3 PUFA ratio play an important role in modifying AD pathophysiology, insulin signaling pathway, and neuro-inflammation response to high fat diet treatment in brain.


2021 ◽  
Author(s):  
Xuling Lv ◽  
Hao Chen ◽  
Zikai Zhang ◽  
Tian Li ◽  
Qing Wei ◽  
...  

Abstract Background: Pelvic floor dysfunction (PFD) is a spectrum of disorders including stress urinary incontinence and pelvic organ prolapse. Transforming growth factor-β1 (TGF-β1) can induce mesenchymal stem cells (MSCs) to differentiate into smooth muscle cells (SMCs). SMCs derived from adipose-derived stem cells (ADSCs) can be used to repair damaged pelvic floor smooth muscle tissues, which is of great interest for clinical applications using stem cell therapy for PFD. The Wnt/β-catenin pathway acts as a decisive factor in the fate of stem cells.Methods and Results: In this study, we used medium containing TGF-β1, TGF-β1 inhibitor LY2109761, or Wnt/β-catenin inhibitor KYA1797K, to induce ADCSs to differentiate into SMCs in vitro to explore the influence of TGF-β1 on the myogenic differentiation of ADCSs via the Wnt/β-catenin pathway. Results: 1) TGF-β1 induces ADSC-derived SMCs to hyper-express the SMC markers including SMA-α, Desmin, Calponin, and SMMHC ; 2) TGF-β1 activates the Wnt/β-catenin signaling pathway in ADSCs. After blocking TGF-β1, the Wnt/β-catenin pathway and myogenic differentiation in cells were inhibited; 3) the Wnt/β-catenin pathway is involved in the differentiation of ADSCs into SMCs. After differentiation induction, the synchronized changes in the activation of Wnt/β-catenin signaling and the expression of SMC-specific proteins showed a trend of simultaneous changes, and after the inhibition of the Wnt pathway, the adult muscle differentiation was significantly inhibited.Conclusions: We established a simpler and more efficient method for inducing ADSCs to differentiate into SMCs using TGF-β1 and demonstrated that the Wnt/β-catenin signaling pathway is activated during this process.


Oncotarget ◽  
2015 ◽  
Vol 6 (33) ◽  
pp. 34475-34493 ◽  
Author(s):  
Andreas Ritter ◽  
Alexandra Friemel ◽  
Friderike Fornoff ◽  
Mouhib Adjan ◽  
Christine Solbach ◽  
...  

2020 ◽  
Author(s):  
Wang Zi Xian ◽  
Liu Qian ◽  
Liu Jian Min ◽  
Zheng Zi Qiong ◽  
Feng Jia ◽  
...  

Abstract BackgroundRegenerative medicine and tissue engineering have brought new therapeutic prospects to the treatment of soft tissue defects, but the selection of seed cells is the key to treatment. Adipose-derived stem cells (ASCs) have always been a popular candidate for seed cells because of their rich sources, easy access, high plasticity, and strong value-added capabilities. The purpose of the current study is to explore the role of PACAP -derived peptide MPAPO on the adipogenic differentiation of ASCs and its molecular mechanism.MethodsThe effect of MPAPO on the proliferation of adipose-derived stem cells were detected by CCK-8 assay and PI single-staining-flow. To reveal the direct effect of MPAPO on the adipogenic differentiation of ASCs, a model of adipogenic differentiation of adipose stem cells was established. In addition, adipogenic differentiation capacity was assessed using Oil-Red-O Staining, Triglyceride (TG) assay and quantification of gene expression. Finally, the relationship between ASCs adipogenic differentiation and the ERK signaling pathway was explored by Western blot.ResultsMPAPO treatment can significantly promote the proliferation of ASCs. In addition, PACAP treatment improves the adipogenic differentiation efficiency of ASCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipogenic-related transcription factors PPARγ and C/EBPα. The mechanism studies showed that MPAPO selectively binds to the PAC1 receptor to promote the adipogenic differentiation of ASCs via activating the ERK signaling pathway.ConclusionsThe present study shows that MPAPO could promote the adipogenic differentiation of ASCs by activating the ERK signaling pathway, and provide relevant experimental evidence for the filling of clinical tissue defects.


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