title: MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network.
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.
authors: 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.
authors: Hongbin
authors: H
authors: Zhang
authors: 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.
authors: Meiping
authors: M
authors: Guan
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Kristy L
authors: KL
authors: Townsend
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Tian Lian
authors: TL
authors: Huang
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Ding
authors: D
authors: An
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Xu
authors: X
authors: Yan
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Ruidan
authors: R
authors: Xue
authors: 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.
authors: Tim J
authors: TJ
authors: Schulz
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Jonathon
authors: J
authors: Winnay
authors: 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.
authors: Marcelo
authors: M
authors: Mori
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Michael F
authors: MF
authors: Hirshman
authors: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors: Karsten
authors: K
authors: Kristiansen
authors: 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.
authors: John S
authors: JS
authors: Tsang
authors: Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Andrew P
authors: AP
authors: White
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Aaron M
authors: AM
authors: Cypess
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors: Laurie J
authors: LJ
authors: Goodyear
authors: 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.
authors: Yu-Hua
authors: YH
authors: Tseng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052437:Adipocytes, Brown / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003080:Cold Temperature; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C583404:MIRN455 microRNA, human; C574091:MIRN455 microRNA, mouse; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C069766:necdin; D006899:Mixed Function Oxygenases; C551240:factor inhibiting hypoxia-inducible factor 1, mouse; C439790:HIF1AN protein, human; D055372:AMP-Activated Protein Kinases
keywords: UCP1; brown adipogenesis; differentiation; metabolism; microRNA