scholarly journals Isoliquiritigenin Enhances the Beige Adipocyte Potential of Adipose-Derived Stem Cells by JNK Inhibition

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5660
Author(s):  
Hanbyeol Moon ◽  
Jung-Won Choi ◽  
Byeong-Wook Song ◽  
Il-Kwon Kim ◽  
Soyeon Lim ◽  
...  

Human adipose-derived stem cells (hASCs) can be isolated from fat tissue and have attracted interest for their potential therapeutic applications in metabolic disease. hASCs can be induced to undergo adipogenic differentiation in vitro by exposure to chemical agents or inductive growth factors. We investigated the effects and mechanism of differentiating hASC-derived white adipocytes into functional beige and brown adipocytes with isoliquiritigenin (ILG) treatment. Here, we showed that hASC-derived white adipocytes could promote brown adipogenesis by expressing both uncoupling protein 1 (UCP1) and PR/SET Domain 16 (PRDM16) following low-dose ILG treatments. ILG treatment of white adipocytes enhanced the expression of brown fat-specific markers, while the expression levels of c-Jun N-terminal kinase (JNK) signaling pathway proteins were downregulated. Furthermore, we showed that the inhibition of JNK phosphorylation contributed to white adipocyte differentiation into beige adipocytes, which was validated by the use of SP600125. We identified distinct regulatory effects of ILG dose responses and suggested that low-dose ILG induced the beige adipocyte potential of hASCs via JNK inhibition.

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1640 ◽  
Author(s):  
Siyu Xie ◽  
Yuan Li ◽  
Wendi Teng ◽  
Min Du ◽  
Yixuan Li ◽  
...  

Promoting white-to-beige adipocyte transition is a promising approach for obesity treatment. Although Liensinine (Lie), a kind of isoquinoline alkaloid, has been reported to affect white-to-beige adipocyte transition, its effects on inhibiting beige adipocytes recovering to white adipocytes and maintaining the characteristics of beige adipocyte remain unclear. Therefore, we explored the effects and underlying mechanism of Lie on beige adipocyte maintenance in vitro and in vivo. Here, we first demonstrated that after white adipocytes turned to beige adipocytes by rosiglitazone (Rosi) stimuli, beige adipocytes gradually lost their characteristics and returned to white adipocytes again once Rosi was withdrawn. We found that Lie retained high levels of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I, II, III, IV and V (COX I–V), oxygen consumption rate (OCR) after Rosi withdrawal. In addition, after Rosi withdrawal, the beige-to-white adipocyte transition was coupled to mitophagy, while Lie inhibited mitophagy flux by promoting the accumulation of pro-cathepsin B (pro-CTSB), pro-cathepsin D (pro-CTSD) and pro-cathepsin L (pro-CTSL), ultimately maintaining the beige adipocytes characteristics in vitro. Moreover, through blocking mitophagy flux, Lie significantly retained the molecular characteristics of beige adipocyte, reduced body weight gain rate and enhanced energy expenditure after stimuli withdrawal in vivo. Together, our data showed that Lie inhibited lysosomal cathepsin activity by promoting the accumulation of pro-CTSB, pro-CTSD and pro-CTSL, which subsequently inhibited mitophagy flux, and ultimately inhibited the beige adipocytes recovering to white adipocytes and maintained the characteristics of beige adipocyte after stimuli withdrawal. In conclusion, by blocking lysosome-mediated mitophagy, Lie inhibits beige adipocytes recovering to white adipocytes and may be a potential candidate for preventing high fat diet induced obesity.


Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1418
Author(s):  
Woo Yong Park ◽  
Gahee Song ◽  
Ja Yeon Park ◽  
Kwan-Il Kim ◽  
Kwang Seok Ahn ◽  
...  

The extract of the Gardenia jasminoides fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms. To investigate the role of GJFE on thermogenesis in mice, we used an acute cold exposure model. After 2 weeks of feeding, the cold tolerance of GJFE-fed mice was notably increased compared to PBS-fed mice. This was due to an increase in thermogenic proteins in the inguinal white adipose tissue of the cold-exposed mice. Moreover, GJFE significantly increased thermogenic factors such as peroxisome proliferator-activated receptor gamma (PPARγ), uncoupling protein 1 (UCP1), and PPARγ coactivator 1 alpha (PGC1α) in vitro as well. Factors related to mitochondrial abundance and functions were also induced by GJFE in white and beige adipocytes. However, the treatment of PPARγ inhibitor abolished the GJFE-induced changes, indicating that activation of PPARγ is critical for the thermogenic effect of GJFE. In conclusion, GJFE induces thermogenic action by activating mitochondrial function via PPARγ activation. Through these findings, we suggest GJFE as a potential anti-obesity agent with a novel mechanism involving thermogenic action in white adipocytes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alona V. Zlatska ◽  
Roman G. Vasyliev ◽  
Inna M. Gordiienko ◽  
Anzhela E. Rodnichenko ◽  
Maria A. Morozova ◽  
...  

2019 ◽  
Vol 47 (12) ◽  
pp. 6303-6314
Author(s):  
Su Wang ◽  
Jian Gao ◽  
Maohuai Wang ◽  
Liquan Chen ◽  
Xiaowei Zhang ◽  
...  

Objective This study investigated the effect of recombinant human connective tissue growth factor (hCTGF) on rat adipose-derived stem cells (ADSCs) and explored the feasibility of using ADSCs to treat pelvic organ prolapse. Methods ADSCs were isolated from rat inguinal adipose tissue and characterized by flow cytometry and for osteogenic and adipogenic differentiation. ADSCs were treated with recombinant hCTGF and qRT-PCR was performed to detect collagen I and III expression on post-treatment days 7, 14, and 28. Osteogenic and adipogenic differentiation of ADSCs was performed to evaluate the effect of hCTGF. ADSCs were seeded in biological grafting materials, acellular porcine pericardium (APP) and acellular bovine pericardium (ABP), then implanted in the rat vagina. Histology was performed to observe inflammation among different groups. Results Collagen I and III expression in ADSCs was significantly increased, and the ability to differentiate into osteogenic and adipogenic lineages was diminished after hCTGF treatment. APP and ABP seeded with ADSCs significantly decreased inflammation and protected from degradation in vivo compared with APP and ABP only; ABP seeded with ADSCs had the lowest inflammation. Conclusion hCTGF regulates collagen I and III expression and induces ADSC differentiation in vitro. ADSCs decrease inflammation associated with APP and ABP in vivo.


2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Bin Sun ◽  
Yongkang Jiang ◽  
Hengqing Cui ◽  
Xia Fang ◽  
Gang Han ◽  
...  

Abstract Macrodactyly is a congenital malformation characterized by enlargement of bone and soft tissues in limbs, typically with excessive accumulation of adipose tissues. Although gain-of-function mutation of PIK3CA has been identified in macrodactyly, the mechanism of PIK3CA mutation in adipose accumulation is poorly understood. In this study, we found that adipocytes from macrodactyly were more hypertrophic than those observed in polydactyly. PIK3CA (H1047R) activating mutation and enhanced activity of PI3K/AKT pathway were detected in macrodactylous adipose-derived stem cells (Mac-ADSCs). Compared to polydactyly-derived ADSCs (Pol-ADSCs), Mac-ADSCs had higher potential in adipogenic differentiation. Knockdown of PIK3CA or inhibition by BYL-719, a potent inhibitor of PIK3CA, impaired adipogenesis of Mac-ADSCs in vitro. In vivo study, either transient treatment of ADSCs or intragastrical gavage with BYL-719 inhibited the adipose formation in patient-derived xenograft (PDX). Furthermore, RNA-seq revealed that E2F1 was up-regulated in Mac-ADSCs and its knockdown blocked the PIK3CA-promoted adipogenesis. Our findings demonstrated that PIK3CA activating mutation promoted adipogenesis of ADSCs in macrodactyly, and that this effect was exerted by the up-regulation of E2F1. This study revealed a possible mechanism for adipose accumulation in macrodactyly and suggested BYL-719 as a potential therapeutic agent for macrodactyly treatment.


2021 ◽  
Vol 54 (03) ◽  
pp. 278-283
Author(s):  
Pallavi Priyadarshini ◽  
Soumi Samuel ◽  
Basan Gowda Kurkalli ◽  
Chethan Kumar ◽  
Basavarajappa Mohana Kumar ◽  
...  

Abstract Background: Adipose-derived stem cells (ADSCs) are the most preferred cell type, based on their phenotypic characteristics, plasticity, and favorable immunological properties for applications in soft-tissue augmentation. Hence, the present in vitro study was aimed to evaluate the adipogenic differentiation potential of human ADSCs upon culturing individually with collagen gel and platelet-rich fibrin (PRF). Materials and methods: The collected lipoaspirate was used for establishing ADSCs using enzymatic digestion method. Then, the cells were analyzed for their morphology, viability, proliferation rate, population doubling time (PDT), colony-forming ability, cell surface markers expression, and osteogenic differentiation as biological properties. Further, ADSCs were evaluated for their adipogenicity using induction media alone, and by culturing with collagen gel and PRF individually for prospective tissue augmentation. Results: ADSCs were successfully established in vitro and exhibited a fibroblast-like morphology throughout the culture period. Cells had higher viability, proliferation potential and showed their ability to form colonies. The positive expression of cell surface markers and osteogenic ability confirmed the potency of ADSCs. The ADSCs cultured on collagen gel and PRF, individually, showed higher number of differentiated adipocytes than ADSCs grown with adipogenic induction medium alone. Conclusion: The extent of lipid accumulation by ADSCs was slightly higher when cultured on collagen gel than on PRF. Additional experiments are required to confirm better suitability of scaffold materials for soft-tissue regeneration.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Mingqi Zhang ◽  
Zhuoshi Wang ◽  
Yan Zhao ◽  
Lirong Zhang ◽  
Ling Xu ◽  
...  

Human eyelid adipose-derived stem cells (HEASCs) are a new source of autologous mesenchymal stem cells, which are derived from neuroectoderm and potentially applied in the tissue regeneration and cell therapies. Based on the prevalence of blepharoplasty in Asia and the availability of HEASCs, we investigated the effect of donor age on their characteristics and regenerative potential of HEASCs in vitro. The HEASCs were isolated from patients of three groups: (1) <20 years (n=4), (2) >20 years, <45 years (n=5), and (3) >55 years (n=4). For each group, the proliferative capacity, colony-forming ability, surface markers, differentiation ability, wound healing function, and secreted protein were contrastively evaluated and quantified for statistical analysis. It was found that HEASCs were successfully isolated and cultured by an explant culture method. The proliferative rates, osteogenic and chondrogenic differentiation potentials, wound healing ability, and the expression of TGF-β1 and fibronectin protein of HEASCs significantly decreased as age increased. However, the expression of CD90 antigen and the adipogenic differentiation showed an age-related increase in HEASCs. As many degenerative diseases increase in prevalence with age, the age-related changes of the HEASCs proliferation potential, differentiation capacity, and wound healing ability should be taken into account whenever they are intended for use in research or cytotherapy.


2020 ◽  
Vol 21 (18) ◽  
pp. 6640
Author(s):  
Mária Szatmári-Tóth ◽  
Abhirup Shaw ◽  
István Csomós ◽  
Gábor Mocsár ◽  
Pamela Fischer-Posovszky ◽  
...  

Thermogenic brown and beige adipocytes oxidize metabolic substrates producing heat, mainly by the mitochondrial uncoupling protein UCP1, and can thus counteract obesity. Masked beige adipocytes possess white adipocyte-like morphology, but can be made thermogenic by adrenergic stimuli. We investigated the regulation of mitophagy upon thermogenic activation of human masked and mature beige adipocytes. Human primary abdominal subcutaneous adipose-derived stromal cells (hASCs) and Simpson–Golabi–Behmel syndrome (SGBS) preadipocytes were differentiated to white and beige adipocytes, then their cAMP-induced thermogenic potential was assessed by detecting increased expressions of UCP1, mitochondrial DNA content and respiratory chain complex subunits. cAMP increased the thermogenic potential of white adipocytes similarly to beige ones, indicating the presence of a masked beige population. In unstimulated conditions, a high autophagic flux and mitophagy rates (demonstrated by LC3 punctae and TOM20 co-immunostaining) were observed in white adipocytes, while these were lower in beige adipocytes. Silencing and gene expression experiments showed that the ongoing mitophagy was Parkin-independent. cAMP treatment led to the downregulation of mitophagy through PKA in both types of adipocytes, resulting in more fragmented mitochondria and increased UCP1 levels. Our data indicates that mitophagy is repressed upon encountering a short-term adrenergic stimulus, as a fast regulatory mechanism to provide high mitochondrial content for thermogenesis.


2020 ◽  
Vol 7 (3) ◽  
pp. 110 ◽  
Author(s):  
Kristen Newman ◽  
Kendra Clark ◽  
Bhuvaneswari Gurumurthy ◽  
Pallabi Pal ◽  
Amol V. Janorkar

This study aimed to probe the effect of formulation of scaffolds prepared using collagen and elastin-like polypeptide (ELP) and their resulting physico-chemical and mechanical properties on the adipogenic differentiation of human adipose derived stem cells (hASCs). Six different ELP-collagen scaffolds were prepared by varying the collagen concentration (2 and 6 mg/mL), ELP addition (6 mg/mL), or crosslinking of the scaffolds. FTIR spectroscopy indicated secondary bonding interactions between collagen and ELP, while scanning electron microscopy revealed a porous structure for all scaffolds. Increased collagen concentration, ELP addition, and presence of crosslinking decreased swelling ratio and increased elastic modulus and compressive strength of the scaffolds. The scaffold characteristics influenced cell morphology, wherein the hASCs seeded in the softer, non-crosslinked scaffolds displayed a spread morphology. We determined that stiffer and/or crosslinked elastin-collagen based scaffolds constricted the spreading of hASCs, leading to a spheroid morphology and yielded an enhanced adipogenic differentiation as indicated by Oil Red O staining. Overall, this study underscored the importance of spheroid morphology in adipogenic differentiation, which will allow researchers to create more physiologically-relevant three-dimensional, in vitro culture models.


Author(s):  
Sreedhar Thirumala ◽  
Jeffrey M. Gimble ◽  
Ram V. Devireddy

Effective techniques for the cryopreservation of human Adipose Stem Cells (ASCs) could increase the usefulness of these cells in tissue engineering and regenerative medicine. The traditional method of using fetal calf serum (FCS) and a chemical cryoprotectant like dimethylsulfoxide (DMSO) during freezing storage restricts the direct use of ASCs in regenerative medicine and reconstruction surgery. The objective of this study was to investigate the apoptotic, necrotic and viability response of ASCs frozen/thawed in the presence of a high molecular weight polymer, Polyvinylpyrrolidone (PVP) and in the absence of FCS. Post-freeze/thaw studies were also conducted to evaluate the effect of PVP on the in vitro osteogenic and adipogenic differentiation of ASCs. The results were compared with those obtained using the most commonly used cryopreservation media of 10%DMSO + 10% Dulbecco’s Modified Eagle Media (DMEM) + 80%FCS.


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