title: MicroRNA-26 family is required for human adipogenesis and drives characteristics of brown adipocytes.
abstract: Adipose tissue contains thermogenic adipocytes (i.e., brown and brite/beige) that oxidize nutrients at exceptionally high rates via nonshivering thermogenesis. Its recent discovery in adult humans has opened up new avenues to fight obesity and related disorders such as diabetes. Here, we identified miR-26a and -26b as key regulators of human white and brite adipocyte differentiation. Both microRNAs are upregulated in early adipogenesis, and their inhibition prevented lipid accumulation while their overexpression accelerated it. Intriguingly, miR-26a significantly induced pathways related to energy dissipation, shifted mitochondrial morphology toward that seen in brown adipocytes, and promoted uncoupled respiration by markedly increasing the hallmark protein of brown fat, uncoupling protein 1. By combining in silico target prediction, transcriptomics, and an RNA interference screen, we identified the sheddase ADAM metallopeptidase domain 17 (ADAM17) as a direct target of miR-26 that mediated the observed effects on white and brite adipogenesis. These results point to a novel, critical role for the miR-26 family and its downstream effector ADAM17 in human adipocyte differentiation by promoting characteristics of energy-dissipating thermogenic adipocytes.
authors.affiliation: RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Karbiener
authors.forename: Didier F
authors.initials: DF
authors.lastname: Pisani
authors.forename: Andrea
authors.initials: A
authors.lastname: Frontini
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Oberreiter
authors.forename: Eleonore
authors.initials: E
authors.lastname: Lang
authors.forename: Alexandros
authors.initials: A
authors.lastname: Vegiopoulos
authors.forename: Karin
authors.initials: K
authors.lastname: Mössenböck
authors.forename: Gerwin A
authors.initials: GA
authors.lastname: Bernhardt
authors.forename: Torsten
authors.initials: T
authors.lastname: Mayr
authors.forename: Florian
authors.initials: F
authors.lastname: Hildner
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
authors.forename: Gérard
authors.initials: G
authors.lastname: Ailhaud
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000378:metabolism / Q000648:ultrastructure; D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D002675:Child, Preschool; D003080:Cold Temperature; D003198:Computer Simulation; D006801:Humans; D007223:Infant; D007473:Ion Channels; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D007473:Ion Channels; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; C528163:MIRN26 microRNA, human; C000604371:UCP1 protein, human; C000606462:ADAM17 protein, human
keywords: ADAM17; Adipocyte differentiation; Brite adipogenesis; MicroRNA-26; White adipogenesis