Human beige adipocytes for drug discovery and cell therapy in metabolic diseases

Singh, Arashdeep; Zhang, Liang; Avery, John; Yin, Amelia; Du, Yuhong; Wang, Hui; Li, Zibo; Fu, Haian; Yin, Hang; Dalton, Stephen

doi:10.1038/s41467-020-16340-3

Cited by 49 publications

(64 citation statements)

References 71 publications

(102 reference statements)

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“…Increasing brown adipose tissue (BAT)-associated gene expression in WAT has emerged as a therapeutic target in obesity [ 31 ] and EPO can promote brown fat-associated gene expression in white adipose tissue of male mice [ 23 ]. EPO treatment in the female ERα−/− mice on the HFD but not in the female WT mice significantly increased the expression of brown fat-like genes, PGC-1α, Cidea, PPAR-α, and PRDM16 ( Figure 4 B).…”

Section: Resultsmentioning

confidence: 99%

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha

Lee

Walter

Korach

et al. 2021

Molecular Metabolism

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Section: Resultsmentioning

confidence: 99%

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha

Lee

Walter

Korach

et al. 2021

Molecular Metabolism

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“…Adipose tissue is classified as WAT, which is a depot of energy storage, and brown adipose tissue (BAT), mainly responsible for thermogenesis and energy expenditure [ 16 , 17 ]. Classic brown adipocytes are characterized with higher numbers of mitochondria whose inner membrane is rich in uncoupling protein 1 (UCP1) and which are activated upon β3-adrenergic stimulation or cold exposure [ 15 , 17 , 19 , 20 , 21 ]. The energy-dissipating ability of BAT could help to recover the energy imbalances resulting from metabolic disorders such as obesity and type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…The energy-dissipating ability of BAT could help to recover the energy imbalances resulting from metabolic disorders such as obesity and type 2 diabetes. Another type of adipocytes—inducible brown-like adipocytes, localized in WAT—was described in recent decades and termed as beige or brown-in-white [ 14 , 16 , 19 , 22 , 23 ]. Cold exposure, β3-adrenergic agonist or prolonged peroxisome proliferator-activated receptor γ (PPARγ) agonist treatment, among other stimuli, trigger the biogenesis of beige adipocytes in WAT depots, also known as browning [ 6 , 17 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…Cold exposure, β3-adrenergic agonist or prolonged peroxisome proliferator-activated receptor γ (PPARγ) agonist treatment, among other stimuli, trigger the biogenesis of beige adipocytes in WAT depots, also known as browning [ 6 , 17 , 23 , 24 , 25 ]. Like BAT, beige adipocytes expend energy in the form of heat, which has resulted in increased interest in the utilization of browning of white adipocytes as an option for cell-based therapy in obesity-related metabolic disorders [ 14 , 18 , 19 , 21 , 26 , 27 ]. Furthermore, pharmacological activation of the transition of white into beige adipocytes has been exploited as a promising approach for the drug-development of novel anti-obesity leads [ 19 , 22 , 25 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Like BAT, beige adipocytes expend energy in the form of heat, which has resulted in increased interest in the utilization of browning of white adipocytes as an option for cell-based therapy in obesity-related metabolic disorders [ 14 , 18 , 19 , 21 , 26 , 27 ]. Furthermore, pharmacological activation of the transition of white into beige adipocytes has been exploited as a promising approach for the drug-development of novel anti-obesity leads [ 19 , 22 , 25 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

Vasileva

Savova

Amirova

et al. 2020

IJMS

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Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.

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Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids

Escudero,

Vaysse,

Eke

et al. 2023

Advanced Science

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Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom‐up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre‐vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self‐organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein‐1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter‐scale beige adipose micro‐tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.

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Human beige adipocytes for drug discovery and cell therapy in metabolic diseases

Cited by 49 publications

References 71 publications

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha

Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids

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