title: SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation.
abstract: White adipose tissue (WAT) is essential for maintaining metabolic function, especially during obesity. The intronic microRNAs miR-33a and miR-33b, located within the genes encoding sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1, respectively, are transcribed in concert with their host genes and function alongside them to regulate cholesterol, fatty acid, and glucose metabolism. SREBP-1 is highly expressed in mature WAT and plays a critical role in promoting in vitro adipocyte differentiation. It is unknown whether miR-33b is induced during or involved in adipogenesis. This is in part due to loss of miR-33b in rodents, precluding in vivo assessment of the impact of miR-33b using standard mouse models. This work demonstrates that miR-33b is highly induced upon differentiation of human preadipocytes, along with SREBP-1. We further report that miR-33b is an important regulator of adipogenesis, as inhibition of miR-33b enhanced lipid droplet accumulation. Conversely, overexpression of miR-33b impaired preadipocyte proliferation and reduced lipid droplet formation and the induction of peroxisome proliferator-activated receptor γ (PPARγ) target genes during differentiation. These effects may be mediated by targeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets. Together, these findings demonstrate a novel role of miR-33b in the regulation of adipocyte differentiation, with important implications for the development of obesity and metabolic disease.
authors.affiliation: Section of Comparative Medicine, Department of Pathology, Program in Integrative Cell Signaling and Neurobiology of Metabolism and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Price
authors.affiliation: Section of Comparative Medicine, Department of Molecular and Cell and Developmental Biology, Program in Integrative Cell Signaling and Neurobiology of Metabolism Program, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Holtrup
authors.affiliation: Department of Surgery, Section of Plastic and Reconstructive Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Kwei
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Section of Comparative Medicine, Department of Molecular and Cell and Developmental Biology, Program in Integrative Cell Signaling and Neurobiology of Metabolism Program, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rodeheffer
authors.affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS, UMR 7284/INSERM U1081, University of Nice-Sophia Antiopolis, Nice, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bianchini
authors.affiliation: Section of Comparative Medicine, Department of Pathology, Program in Integrative Cell Signaling and Neurobiology of Metabolism and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suárez
authors.affiliation: Section of Comparative Medicine, Department of Pathology, Program in Integrative Cell Signaling and Neurobiology of Metabolism and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and Cell Biology, New York University School of Medicine, New York, New York, USA carlos.fernandez@yale.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000166:cytology*; D056426:Genetic Loci; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
chemical_list: C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D051780:Sterol Regulatory Element Binding Protein 1
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