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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.

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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.
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:



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.


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.


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.


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.


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

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