Regulation of Early Adipose Commitment by Zfp521

Kang, Sona; Åkerblad, Peter; Kiviranta, Riku; Gupta, Rana K.; Kajimura, Shingo; Griffin, Michael; Min, Jie; Baron, Roland; Rosen, Evan D.

doi:10.1371/journal.pbio.1001433

Cited by 112 publications

(127 citation statements)

References 45 publications

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“…Overexpression of Zfp423 in NIH 3T3 fibroblasts was sufficient to confer adipogenic potential in vitro (Gupta et al, 2010). A close paralog to Zfp423 is Zfp521, an established negative regulator of preadipocyte commitment (Kang et al, 2012). Overexpression of Zfp521 in multipotent C3H10T1/2 cells inhibited adipogenesis, whereas knockdown of Zfp521 had the opposite effect (Kang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…A close paralog to Zfp423 is Zfp521, an established negative regulator of preadipocyte commitment (Kang et al, 2012). Overexpression of Zfp521 in multipotent C3H10T1/2 cells inhibited adipogenesis, whereas knockdown of Zfp521 had the opposite effect (Kang et al, 2012). Furthermore, Zfp521 knockout embryos exhibited enlarged BAT and increased white adipocyte numbers at E18.5.…”

Section: Discussionmentioning

confidence: 99%

“…These factors include zinc-finger protein 423 (Zfp423) and early B cell factor 1 (Ebf1), which physically interact with each other and induce Pparg and Cebpa expression (Åkerblad et al, 2002;Festa et al, 2011;Fretz et al, 2010;Gupta et al, 2010;Jimenez et al, 2007). A third factor, Zfp521, exerts an antiadipogenic role by interacting with Ebf1 to inhibit the Zfp423-Ebf1 functional complex and possibly by also inhibiting Zfp423 expression (Kang et al, 2012). We assessed the expression of these early-acting factors in control and mutant ingWAT.…”

Section: Molecular Defects In Sox2-v561d Adipose Tissuementioning

confidence: 99%

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PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

2017

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Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFRα is a marker of adipocyte precursors, and increased PDGFRα activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRα during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRα activity (V561D or D842V), we found that PDGFRα activation inhibits embryonic white adipose tissue organogenesis in a tissue-autonomous manner. By lineage tracing analysis, we also found that collagen-expressing precursor fibroblasts differentiate into white adipocytes in the embryo. PDGFRα inhibited the formation of adipocytes from these precursors while favoring the formation of stromal fibroblasts. This imbalance between adipocytes and stromal cells was accompanied by overexpression of the cell fate regulator Zfp521. PDGFRα activation also inhibited the formation of juvenile beige adipocytes in the inguinal fat pad. Our data highlight the importance of balancing stromal versus adipogenic cell expansion during white adipose tissue development, with PDGFRα activity coordinating this crucial process in the embryo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Molecular Defects In Sox2-v561d Adipose Tissuementioning

confidence: 99%

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PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

2017

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“…The gene was found to present lower methylation levels in IR than in IS patients in association with increased transcription levels. Even though the functional association with the development of IR or T2D remains to be elucidated, future exploration of the role of this gene could reveal a novel mechanism involved in the development of IR and T2D in line with other zinc finger proteins, which are associated with adipogenesis, 37,38 T2D, or insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects

Crujeiras

Díaz‐Lagares

Moreno-Navarrete

et al. 2016

Translational Research

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“…These cells have a high adipogenic potential in vitro and in vivo and express the zinc finger protein 423 (ZFP423), a transcription factor involved in preadipocyte determination in vivo (Gupta et al, 2010;Gupta et al, 2012). Recently it has been shown that another transcription factor, zinc finger protein 521 (ZFP521), can regulate adipocyte development by inhibiting the expression of ZFP423 (Kang et al, 2012).…”

Section: Development Of Vertebrate Adipose Tissuementioning

confidence: 99%

A comparative perspective on lipid storage in animals

Birsoy

Festuccia

Laplante

2013

Journal of Cell Science

120

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SummaryLipid storage is an evolutionary conserved process that exists in all organisms from simple prokaryotes to humans. In Metazoa, longterm lipid accumulation is restricted to specialized cell types, while a dedicated tissue for lipid storage (adipose tissue) exists only in vertebrates. Excessive lipid accumulation is associated with serious health complications including insulin resistance, type 2 diabetes, cardiovascular diseases and cancer. Thus, significant advances have been made over the last decades to dissect out the molecular and cellular mechanisms involved in adipose tissue formation and maintenance. Our current understanding of adipose tissue development comes from in vitro cell culture and mouse models, as well as recent approaches to study lipid storage in genetically tractable lower organisms. This Commentary gives a comparative insight into lipid storage in uni-and multi-cellular organisms with a particular emphasis on vertebrate adipose tissue. We also highlight the molecular mechanisms and nutritional signals that regulate the formation of mammalian adipose tissue.

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Regulation of Early Adipose Commitment by Zfp521

Abstract: Zfp521 is a novel antiadipogenic transcription factor that helps to determine the identity of a mesenchymal cell as bone or fat.

Cited by 112 publications

References 45 publications

PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects

A comparative perspective on lipid storage in animals

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