title: miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function.
abstract: OBJECTIVE
  In rodents and humans, besides brown adipose tissue (BAT), islands of thermogenic adipocytes, termed "brite" (brown-in-white) or beige adipocytes, emerge within white adipose tissue (WAT) after cold exposure or β3-adrenoceptor stimulation, which may protect from obesity and associated diseases. microRNAs are novel modulators of adipose tissue development and function. The purpose of this work was to characterize the role of microRNAs in the control of brite adipocyte formation.
  
  
  RESULTS
  Using human multipotent adipose derived stem cells, we identified miR-125b-5p as downregulated upon brite adipocyte formation. In humans and rodents, miR-125b-5p expression was lower in BAT than in WAT. In vitro, overexpression and knockdown of miR-125b-5p decreased and increased mitochondrial biogenesis, respectively. In vivo, miR-125b-5p levels were downregulated in subcutaneous WAT and interscapular BAT upon β3-adrenergic receptor stimulation. Injections of an miR-125b-5p mimic and LNA inhibitor directly into WAT inhibited and increased β3-adrenoceptor-mediated induction of UCP1, respectively, and mitochondrial brite adipocyte marker expression and mitochondriogenesis.
  
  
  CONCLUSIONS
  Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Giroud
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Didier F
authors.initials: DF
authors.lastname: Pisani
authors.affiliation: Department of Phoniatrics, ENT University Hospital, Medical University Graz, Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Karbiener
authors.affiliation: Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Barquissau
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Rayane A
authors.initials: RA
authors.lastname: Ghandour
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tews
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chambard
authors.affiliation: Department of General and Visceral Surgery, Ulm University Surgery Center, D-89075 Ulm, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
authors.affiliation: Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Niemi
authors.affiliation: Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Taittonen
authors.affiliation: Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland; Turku University Hospital, Turku, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany; Molecular Metabolic Control, Medical Faculty, Technical University Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland; Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
authors.affiliation: Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany; Molecular Metabolic Control, Medical Faculty, Technical University Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France. Electronic address: amri@unice.fr.
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
keywords: Brite adipocyte; Mitochondriogenesis; White adipocyte; miR-125b-5p