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Metabolism. 2014 Feb;63(2):272-82. doi: 10.1016/j.metabol.2013.10.004. Epub 2013 Oct 24.

MiR-27 orchestrates the transcriptional regulation of brown adipogenesis.

Author information

1
Duke-NUS Medical School Singapore, 8 College Rd, 169857, Singapore; Institute of Molecular and Cell Biology (IMCB), Agency for Science,Technology and Research, 61 Biopolis Drive, 138673, Singapore.
2
University of Geneva, Medical Faculty, Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), 1211 Geneva 4, Switzerland; University College London (UCL), Division of Biosciences, School of Life and Medical Sciences, Institute of Structural and Molecular Biology, Darwin Building, Gower Street, WC1E 6BT, London, UK. Electronic address: Mirko.Trajkovski@unige.ch.

Abstract

OBJECTIVE:

Brown adipose tissue (BAT) produces heat using chemical energy of lipids and glucose, a function induced by cold exposure or diet. The brown adipogenesis is tightly controlled in a coordinated interplay between several transcriptional factors. It is not known what enables and coordinates this robust program of concerted cooperation between the transcriptional factors and co-regulators necessary for the brown adipogenesis.

MATERIALS/METHODS:

A. In vivo studies--we investigated the expression levels of miR-27a and b in mice after cold exposure. B. Using gene expression and functional studies together with high throughput imaging in primary preadipocytes, and cell culture models, we investigated the role of miR-27 in beige and brown adipogenesis. C. Using gene silencing and rescue experiments we dissected the molecular mechanisms of the miR-27 action.

RESULTS:

After cold exposure, miR-27 is downregulated in BAT and subcutaneous white adipose tissue (SAT). MiR-27 is also downregulated during brown adipogenesis of primary preadipocytes in vitro, and it directly targets and negatively regulates the essential components of the brown transcriptional network: Prdm16, Pparα, Creb, and in part Pgc1β. Together with its direct effect on Pparγ, and indirect on Pgc1α, mir-27 decreases brown differentiation of cultured cells and of primary SAT preadipocytes.

CONCLUSIONS:

Our results point to miR-27 as a central upstream regulator of the transcriptional network involved in beige and brown adipogenesis after cold exposure, and suggest miR-27 inhibition as a novel therapeutic approach for metabolic diseases aiming at increasing the beige/brown fat mass.

KEYWORDS:

3′ untranslated region; 3′UTR; Adipocyte protein 2 (Fabp4, Fatty acid binding protein 4); Adipogenesis; Adrb3; BAT; Beige; Brown; Brown adipose tissue; C/EBPs; CCAAT/enhancer-binding proteins; Creb; Cyclic adenosine monophosphate; Fat; IBMX; Mouse Primary Immortalized Brown Adipocytes; Myf5; Myogenic factor 5; OCR; PIBA; PPARγ-coactivators-1; PRDI-BF1-RIZ1 (PR) domain containing 16; Peroxisome proliferator-activated receptor-a and γ; Pgc1; Pparα and γ; Prdm16; SAT; SVF; Subcutaneous adipose tissue; Ucp1; Uncoupling protein 1; VAT; Visceral adipose tissue; WAT; White adipose tissue; aP2; beta-3 adrenergic receptor; cAMP; cAMP responsive element binding protein; isobutylmethylxanthine; miRNAs; microRNAs; oxygen consumption rates; primary stromal–vascular fraction

PMID:
24238035
DOI:
10.1016/j.metabol.2013.10.004
[Indexed for MEDLINE]

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