title: miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit.
abstract: Brown adipocytes are a primary site of energy expenditure and reside not only in classical brown adipose tissue but can also be found in white adipose tissue. Here we show that microRNA 155 is enriched in brown adipose tissue and is highly expressed in proliferating brown preadipocytes but declines after induction of differentiation. Interestingly, microRNA 155 and its target, the adipogenic transcription factor CCAAT/enhancer-binding protein β, form a bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation. Inhibition of microRNA 155 enhances brown adipocyte differentiation and induces a brown adipocyte-like phenotype ('browning') in white adipocytes. Consequently, microRNA 155-deficient mice exhibit increased brown adipose tissue function and 'browning' of white fat tissue. In contrast, transgenic overexpression of microRNA 155 in mice causes a reduction of brown adipose tissue mass and impairment of brown adipose tissue function. These data demonstrate that the bistable loop involving microRNA 155 and CCAAT/enhancer-binding protein β regulates brown lineage commitment, thereby, controlling the development of brown and beige fat cells.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Franziska
authors.initials: F
authors.lastname: Siegel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kipschull
authors.forename: Bodo
authors.initials: B
authors.lastname: Haas
authors.forename: Holger
authors.initials: H
authors.lastname: Fröhlich
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D025461:Feedback, Physiological; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D053773:Transforming Growth Factor beta1