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EMBO Rep. 2015 Oct;16(10):1378-93. doi: 10.15252/embr.201540837. Epub 2015 Aug 24.

MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network.

Author information

1
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark hongbin@sund.ku.dk yu-hua.tseng@joslin.harvard.edu.
2
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
3
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
4
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Adipocyte Development Research Group, German Institute of Human Nutrition, Potsdam, Germany.
5
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil.
6
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
7
Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases (NIAID) and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD, USA.
8
Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
9
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA hongbin@sund.ku.dk yu-hua.tseng@joslin.harvard.edu.

Abstract

Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.

KEYWORDS:

UCP1; brown adipogenesis; differentiation; metabolism; microRNA

PMID:
26303948
PMCID:
PMC4766451
DOI:
10.15252/embr.201540837
[Indexed for MEDLINE]
Free PMC Article

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