Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation
Authors
Huang, LeiPan, Dongning
Chen, Qingbo
Zhu, Lihua (Julie)
Ou, Jianhong
Wabitsch, Martin
Wang, Yong-Xu
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDocument Type
Journal ArticlePublication Date
2017-07-12Keywords
Energy metabolismFat metabolism
Mechanisms of disease
Transcription
Biochemistry, Biophysics, and Structural Biology
Cellular and Molecular Physiology
Genetics and Genomics
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Show full item recordAbstract
Browning of subcutaneous white fat (iWAT) involves several reprograming events, but the underlying mechanisms are incompletely understood. Here we show that the transcription factor Hlx is selectively expressed in brown adipose tissue (BAT) and iWAT, and is translationally upregulated by beta3-adrenergic signaling-mediated suppression of the translational inhibitor 4E-BP1. Hlx interacts with and is co-activated by Prdm16 to control BAT-selective gene expression and mitochondrial biogenesis. Hlx heterozygous knockout mice have defects in brown-like adipocyte formation in iWAT, and develop glucose intolerance and high fat-induced hepatic steatosis. Conversely, transgenic expression of Hlx at a physiological level drives a full program of thermogenesis and converts iWAT to brown-like fat, which improves glucose homeostasis and prevents obesity and hepatic steatosis. The adipose remodeling phenotypes are recapitulated by fat-specific injection of Hlx knockdown and overexpression viruses, respectively. Our studies establish Hlx as a powerful regulator for systematic white adipose tissue browning and offer molecular insights into the underlying transcriptional mechanism.The transcriptional co-activator Prdm16 regulates browning of white adipose tissue (WAT). Here, the authors show that Prdm16 interacts with the transcription factor Hlx, which is stabilized in response to beta3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT.Source
Nat Commun. 2017 Jul 12;8(1):68. doi: 10.1038/s41467-017-00098-2. Link to article on publisher's siteDOI
10.1038/s41467-017-00098-2Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40409PubMed ID
28701693Related Resources
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© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/s41467-017-00098-2
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Except where otherwise noted, this item's license is described as © The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.