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Nat Commun. 2017 Jul 12;8(1):68. doi: 10.1038/s41467-017-00098-2.

Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation.

Author information

1
Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
2
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Endocrinology and Diabetes, University Medical Center Ulm, Ulm, 89075, Germany.
3
Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA. yongxu.wang@umassmed.edu.

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 β3-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 β3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT.

PMID:
28701693
PMCID:
PMC5507986
DOI:
10.1038/s41467-017-00098-2
[Indexed for MEDLINE]
Free PMC Article

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