Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation - PubMed (original) (raw)

Review

. 2015 Jul;64(7):2369-75.

doi: 10.2337/db15-0203. Epub 2015 Jun 7.

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Review

Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation

Patrick Seale. Diabetes. 2015 Jul.

Abstract

Brown and beige adipose tissue is specialized for heat production and can be activated to reduce obesity and metabolic dysfunction in animals. Recent studies also have indicated that human brown fat activity levels correlate with leanness. This has revitalized interest in brown fat biology and has driven the discovery of many new regulators of brown fat development and function. This review summarizes recent advances in our understanding of the transcriptional mechanisms that control brown and beige fat cell development.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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Figures

Figure 1

Figure 1

Transcriptional regulation of brown fat cell differentiation and activation. EBF2 marks committed brown preadipocytes and may regulate the commitment process from upstream stem cells. EWS/YBX1 regulates BMP7 production, which then acts in an autocrine manner to induce brown adipogenesis. EBF2, PRDM16, and ZFP516 specifically regulate the induction of brown fat–specific genes during the differentiation process. PRDM16 coactivates c/EBPβ, PPARγ, PPARα, thyroid receptor (TR), and ZFP516. Upon cold exposure/β-adrenergic agonist treatment, brown fat cells are activated to undergo thermogenesis and increase their expression of thermogenic genes. IRF4 plays a major role in this process through recruiting the PGC-1α coactivator. PGC-1α can also coactivate PPARs and TR to activate the transcription of thermogenic genes.

Figure 2

Figure 2

Model for transcriptional regulation of brown fat–selective genes through EBF2 and PRDM16. A: EBF2 binds to enhancer regions of brown fat genes at early time points during brown fat cell differentiation. B: Once bound, EBF2 facilitates the binding of PPARγ and other transcription factors to these enhancer regions. C: PRDM16 is recruited to these sites indirectly, likely through c/EBPβ, PPARγ, and/or ZFP516. PRDM16 binds and recruits the MED1/Mediator complex to facilitate enhancer/promoter looping and preinitiation complex (PIC) assembly. This action of PRDM16 is required to promote the efficient transcription of brown fat genes.

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