Inflammatory Signaling and Brown Fat Activity

Omran, Farah; Christian, Mark

doi:10.3389/fendo.2020.00156

Cited by 63 publications

(57 citation statements)

References 218 publications

(172 reference statements)

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“…As the cellular model aimed to recapitulate the developmental steps undergone during brown adipogenesis, we validated the temporal expression of known BAT regulators, markers, and other functionally relevant proteins in humans ( Omran and Christian, 2020 ; Perdikari et al., 2018 ). This analysis revealed that C/EBPα , C/EBPβ , and PRDM16 , for example, are already upregulated in the adipose progenitor state (D8).…”

Section: Resultsmentioning

confidence: 99%

Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

et al. 2021

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Summary Increasing brown adipose tissue (BAT) mass and activation is a therapeutic strategy to treat obesity and complications. Obese and diabetic patients possess low amounts of BAT, so an efficient way to expand their mass is necessary. There is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Accessing human BAT is challenging, given its low volume and anatomical dispersion. These constraints make detailed BAT-related developmental and functional mechanistic studies in humans virtually impossible. We have developed and characterized functionally and molecularly a new chemically defined protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs) that overcomes current limitations. This protocol recapitulates step by step the physiological developmental path of human BAT. The BAs obtained express BA and thermogenic markers, are insulin sensitive, and responsive to β-adrenergic stimuli. This new protocol is scalable, enabling the study of human BAs at early stages of development.

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Section: Resultsmentioning

confidence: 99%

Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

et al. 2021

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“…Pro-inflammatory signals are important players of the BAT and beige adipocytes thermogenesis. Many inflammatory cells and pro-inflammatory cytokines secreted by both immune cells and adipocytes can negatively affect the thermogenic activation and browning of WAT ( 198 ). As it has been commented above, p38 controls the expression of many pro-inflammatory cytokines by macrophages ( 199 ) and also controls the secretion of the M2 chemokine CXCL14 ( 188 ).…”

Section: Role Of P38 In Adipose Tissue Inflammationmentioning

confidence: 99%

Uncovering the Role of p38 Family Members in Adipose Tissue Physiology

et al. 2020

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The complex functions of adipose tissue have been a focus of research interest over the past twenty years. Adipose tissue is not only the main energy storage depot, but also one of the largest endocrine organs in the body and carries out crucial metabolic functions. Moreover, brown and beige adipose depots are major sites of energy expenditure through the activation of adaptive, non-shivering thermogenesis. In recent years, numerous signaling molecules and pathways have emerged as critical regulators of adipose tissue, in both homeostasis and obesity-related disease. Among the best characterized are members of the p38 kinase family. The activity of these kinases has emerged as a key contributor to the biology of the white and brown adipose tissues, and their modulation could provide new therapeutic approaches against obesity. Here, we give an overview of the roles of the distinct p38 family members in adipose tissue, focusing on their actions in adipogenesis, thermogenic activity, and secretory function.

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“…As the cellular model is supposed to recapitulate the developmental steps undergone during brown adipogenesis, we validated the temporal expression of some of the known brown adipose tissue regulators, markers, and other functionally relevant proteins in humans 36,37 . This analysis unveiled that C/EBP α, C/EBP β, and PRDM16 , for example, are already upregulated in the adipose progenitor state (D8) Another transcriptional regulator such as CIDEC and PPARγ are, as could be anticipated, are specifically upregulated later in the differentiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Unravelling the developmental roadmap towards human brown adipose tissue

Carobbio

Guénantin

Bahri

et al. 2020

Preprint

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Increasing brown adipose tissue (BAT) mass and activation has been proposed as a potential therapeutic strategy to treat obesity and associated cardiometabolic complications. Given that obese and diabetic patients possess low amounts of BAT, an efficient way to expand their BAT mass would be necessary if BAT is to be useful. Currently, there is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Moreover, to have access to human BAT is challenging, given its low volume and being anatomically dispersed. These constrain makes detailed mechanistic studies related to BAT development and function in humans virtually impossible. To overcome these limitations, we have developed a human-relevant new protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs). Unique to this protocol is that it is chemically-defined to recapitulate a physiological step-by-step developmental path of BAT that captures transient paraxial mesoderm and BAT progenitor states, on its way to reaching the adipocyte stage finally. These hPSC-derived BAs express brown adipocyte and thermogenic markers, are insulin sensitive, and respond to β-adrenergic stimuli. This new protocol is a scalable tool to study human BAs during development.

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Inflammatory Signaling and Brown Fat Activity

Cited by 63 publications

References 218 publications

Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

Uncovering the Role of p38 Family Members in Adipose Tissue Physiology

Unravelling the developmental roadmap towards human brown adipose tissue

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