title: Let-7i-5p represses brite adipocyte function in mice and humans.
abstract: In response to cold or β3-adrenoreceptor stimulation brown adipose tissue (BAT) promotes non-shivering thermogenesis, leading to energy dissipation. BAT has long been thought to be absent or scarce in adult humans. The recent discovery of thermogenic brite/beige adipocytes has opened the way to development of novel innovative strategies to combat overweight/obesity and associated diseases. Thus it is of great interest to identify regulatory factors that govern the brite adipogenic program. Here, we carried out global microRNA (miRNA) expression profiling on human adipocytes to identify miRNAs that are regulated upon the conversion from white to brite adipocytes. Among the miRNAs that were differentially expressed, we found that Let-7i-5p was down regulated in brite adipocytes. A detailed analysis of the Let-7i-5p levels showed an inverse expression of UCP1 in murine and human brite adipocytes both in vivo and in vitro. Functional studies with Let-7i-5p mimic in human brite adipocytes in vitro revealed a decrease in the expression of UCP1 and in the oxygen consumption rate. Moreover, the Let-7i-5p mimic when injected into murine sub-cutaneous white adipose tissue inhibited partially β3-adrenergic activation of the browning process. These results suggest that the miRNAs Let-7i-5p participates in the recruitment and the function of brite adipocytes.
authors.affiliation: Univ. Nice Sophia Antipolis, iBV, UMR 7277, Nice, 06100, France.|CNRS, iBV UMR 7277, 06100 Nice, 06100, France.|Inserm, iBV, U1091, 06100 Nice, 06100, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Giroud
authors.affiliation: Department of Phoniatrics, ENT University Hospital, Medical University, Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Karbiener
authors.affiliation: Univ. Nice Sophia Antipolis, iBV, UMR 7277, Nice, 06100, France.|CNRS, iBV UMR 7277, 06100 Nice, 06100, France.|Inserm, iBV, U1091, 06100 Nice, 06100, France.
authors.forename: Didier F
authors.initials: DF
authors.lastname: Pisani
authors.affiliation: Univ. Nice Sophia Antipolis, iBV, UMR 7277, Nice, 06100, France.|CNRS, iBV UMR 7277, 06100 Nice, 06100, France.|Inserm, iBV, U1091, 06100 Nice, 06100, France.
authors.forename: Rayane A
authors.initials: RA
authors.lastname: Ghandour
authors.affiliation: Univ. Nice Sophia Antipolis, iBV, UMR 7277, Nice, 06100, France.|CNRS, iBV UMR 7277, 06100 Nice, 06100, France.|Inserm, iBV, U1091, 06100 Nice, 06100, France.
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Beranger
authors.affiliation: Department of Surgery, Turku University Hospital, Turku, 20521, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Niemi
authors.affiliation: Department of Anesthesiology, Turku University Hospital, Turku, 20521, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Taittonen
authors.affiliation: Turku PET Centre, University of Turku, Turku, 20521, Finland.|Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Turku PET Centre, University of Turku, Turku, 20521, Finland.|Department of Endocrinology, Turku University Hospital, Turku, 20521, 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, iBV, UMR 7277, Nice, 06100, France.|CNRS, iBV UMR 7277, 06100 Nice, 06100, France.|Inserm, iBV, U1091, 06100 Nice, 06100, France.
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
mesh_terms: D000069797:Adipocytes, Beige / Q000378:metabolism* / Q000502:physiology; D052437:Adipocytes, Brown / Q000378:metabolism / Q000502:physiology; D050156:Adipogenesis / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D000071256:Uncoupling Protein 1 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1