A pivotal role of AMPK signaling in medicarpin‐mediated formation of brown and beige

Imran, Khan Mohammad; Yoon, Dahyeon; Kim, Yong-Sik

doi:10.1002/biof.1392

Cited by 26 publications

(13 citation statements)

References 47 publications

(73 reference statements)

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“…Our gene knockdown and competitive chemical inhibition experiments revealed that the upregulation of thermogenesis‐related genes and mitochondrial‐biogenesis–related genes were mediated by AMPK signaling in BioA‐treated cells. It has been reported that AMPK plays a pivotal role in differentiation and function of brown or beige adipocytes from mesenchymal stem cells (Abdul‐Rahman et al, 2016; Imran et al, 2017; Imran, Yoon, & Kim, 2018; Jeong et al, 2017; Nagy et al, 2019). A stimulation of AMPK signals results in SIRT1 mediated deacetylation of PPARγ that engenders a brown‐fat like features and consequently improves mitochondrial biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Biochanin A induces a brown‐fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells

Rahman

Imran

Hossain

et al. 2020

Phytotherapy Research

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In this study, we investigated the effect of Biochanin A (BioA), an O‐methylated isoflavone on the brown‐fat phenotype formation and on the associated thermogenic program including mitochondrial biogenesis and lipolysis in C3H10T1/2 MSCs. Our data demonstrates that Treatment with BioA in an adipogenic differentiation cocktail induced formation of brown‐fat–like adipocytes from C3H10T1/2 MSCs without treatment with a known browning inducer (rosiglitazone or T3) at an early stage of differentiation. The formation of brown‐fat–like adipocytes by BioA treatment was evidenced by upregulation of key thermogenic markers: Ucp1, Pgc1α, Prdm16, and Pparγ. BioA also increased the expression of beige (Cd137 and Fgf21) and brown (Elovl3 and Zic1)‐specific markers. Additionally, BioA treatment promoted mitochondrial biogenesis, judging by the upregulation of genes; Cox8b, Cidea, Dio2, Sirt1, Opa1, and Fis1. BioA treatment increased the amount of mitochondrial DNA and its encoded proteins: oxidative phosphorylation complexes (I–V); this change was associated with high oxygen consumption by C3H10T1/2 MSCs. A small‐interfering‐RNA–induced gene knockdown and experiments with dorsomorphin‐driven competitive inhibition revealed that BioA exerts the thermogenic action via activation of AMPK signaling. Our study shows the mechanism of BioA‐induced promotion of a brown‐fat phenotype. Nonetheless, clinical research is necessary to validate BioA as a brown‐fat‐like signature inducer.

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Section: Discussionmentioning

confidence: 99%

Biochanin A induces a brown‐fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells

Rahman

Imran

Hossain

et al. 2020

Phytotherapy Research

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“…Total RNA was extracted from each sample as described elsewhere ( 26 ). An RNA-Sequencing library was generated using Nextflex Rapid Directional qRNA-Seq Kit according to user’s instruction manual (Bioo Scientific, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Medicarpin induces lipolysis via activation of Protein Kinase A in brown adipocytes

et al. 2018

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Natural pterocarpan Medicarpin (Med) has been shown to have various beneficial biological roles, including inhibition of osteoclastogenesis, stimulation of bone regeneration and induction of apoptosis. However, the effect of the Med on lipolysis in adipocytes has not been reported. Here, we show the effect of Med on lipolysis in different mouse adipocytes and elucidate the underlying mechanism. We observed that Med treatment promoted release of glycerol in the media. Differentiated mouse brown adipose tissue cells were treated with Med. RNA-Seq analysis was performed to elucidate the effect of med and subsequently was confirmed by qRT-PCR and western blotting analyses. Med treatment increased both protein and gene expression levels of hormone-sensitive lipase (Hsl) and adipose triglyceride lipase (Atgl), which are two critical enzymes necessary for lipolysis. Mechanistic study showed that Med activates Protein Kinase A (PKA) and phosphorylates Hsl at PKA target position at Serine660. Silencing of PKA gene by short interfering RNA attenuated the Med-induced increase in glycerol release and Hsl phosphorylation. The results unveil that Med boosts lipolysis via a PKA-dependent pathway in adipocytes and may provide a possible avenue of further research of Med mediated reduction of body fat.

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“…Likewise, THSG, a glycoside of resveratrol, enhanced self-renewal of human dental pulp stem cells via an AMPK signaling pathway [ 105 ]. Evidences showed that medicarpin and cryptotanshinone promoted the differentiation of C3H10T1/2 mesenchymal stem cells into brown adipocytes by increasing the expression of thermogenesis marker uncoupling protein 1 (UCP1), upregulating brown fat-specific markers, and reducing the expression of white fat markers, which were associated with the activation of AMPK pathway [ 106 , 107 ].…”

Section: Signaling Pathways In Stem Cell Differentiation Activatedmentioning

confidence: 99%

Effect of Active Ingredients of Chinese Herbal Medicine on the Rejuvenation of Healthy Aging: Focus on Stem Cells

Wang

Ling

2020

Evidence-Based Complementary and Alternative Medicine

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Stem cells (SCs) are special types of cells with the ability of self-renewal and multidirectional differentiation. As the organism ages, the ability to maintain homeostasis and regeneration deteriorates and the number and activity of stem cells decline. Theoretically, the restoration of stem cells might reverse aging. However, due to their own aging, donor-derived immune rejection, and difficulties in stem cell differentiation control, a series of problems need to be solved to realize the potential for clinical application of stem cells. Chinese herbal medicine is a nature drug library which is suitable for the long-term treatment of aging-related diseases. Modern pharmacological studies have revealed that many active ingredients of Chinese herbal medicines with the effect of promoting stem cells growth and differentiation mainly belong to “reinforcing herbs.” In recent years, exploration of natural active ingredients from Chinese herbal medicines for delaying aging, improving the stem cell microenvironment, and promoting the proliferation and differentiation of endogenous stem cells has attracted substantial attention. This article will focus on active ingredients from Chinese herbs-mediated differentiation of stem cells into particular cell type, like neural cells, endothelial cells, cardiomyocytes, and osteoblasts. We will also discuss the effects of these small molecules on Wnt, Sonic Hedgehog, Notch, eNOS-cGMP, and MAP kinase signal transduction pathways, as well as reveal the role of estrogen receptor α and PPAR γ on selectively promoting or inhibiting stem cells differentiation. This review will provide new insights into the health aging strategies of active ingredients in Chinese herbal medicine in regenerative medicine.

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A pivotal role of AMPK signaling in medicarpin‐mediated formation of brown and beige

Cited by 26 publications

References 47 publications

Biochanin A induces a brown‐fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells

Biochanin A induces a brown‐fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells

Medicarpin induces lipolysis via activation of Protein Kinase A in brown adipocytes

Effect of Active Ingredients of Chinese Herbal Medicine on the Rejuvenation of Healthy Aging: Focus on Stem Cells

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