UMMS Affiliation
Department of Molecular, Cell and Cancer Biology
Publication Date
2017-07-12
Document Type
Article
Disciplines
Biochemistry, Biophysics, and Structural Biology | Cellular and Molecular Physiology | Genetics and Genomics
Abstract
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.
Keywords
Energy metabolism, Fat metabolism, Mechanisms of disease, Transcription
Rights and Permissions
© 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.
DOI of Published Version
10.1038/s41467-017-00098-2
Source
Nat Commun. 2017 Jul 12;8(1):68. doi: 10.1038/s41467-017-00098-2. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
28701693
Repository Citation
Huang L, Pan D, Chen Q, Zhu L(, Ou J, Wabitsch M, Wang Y. (2017). Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation. Open Access Articles. https://doi.org/10.1038/s41467-017-00098-2. Retrieved from https://escholarship.umassmed.edu/oapubs/3214
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cellular and Molecular Physiology Commons, Genetics and Genomics Commons