title: MicroRNA-193b Controls Adiponectin Production in Human White Adipose Tissue.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. In white adipose tissue (WAT), recent studies suggest that miRNA levels are altered in various metabolic diseases, including obesity.
  
  
  OBJECTIVE
  The objective of the study was to determine whether adipocyte-expressed miRNAs altered by obesity can regulate adiponectin expression/secretion in fat cells.
  
  
  METHODS
  Eleven miRNAs previously shown to be altered in obese human WAT were overexpressed in human in vitro-differentiated adipocytes followed by assessments of adiponectin levels in conditioned media.
  
  
  METHODS
  This was cohort study (n = 56) in an academic hospital.
  
  
  METHODS
  Subcutaneous WAT was obtained from nonobese and obese individuals.
  
  
  METHODS
  There were no interventions in this study.
  
  
  METHODS
  Protein and mRNA levels of adiponectin were measured.
  
  
  RESULTS
  Of the 11 investigated miRNAs, three (miR-193b/-126/-26a) increased adiponectin secretion when overexpressed in human adipocytes. However, in human WAT only miR-193b expression correlated with adiponectin gene expression and homeostasis model assessment of insulin resistance. Moreover, quantitative PCR of miR-193b in both WAT and isolated adipocytes showed a significant association with serum adiponectin levels. Overexpression of miR-193b altered the gene expression of seven known adiponectin regulators. 3'-untranslated region reporter assays confirmed binding to cAMP-responsive element binding protein 5, nuclear receptor interacting protein 1, and nuclear transcription factor Yα. The effects of miR-193b on nuclear transcription factor Yα expression were confirmed at the protein level. Transfection with individual miRNA target protectors selective for nuclear transcription factor Yα and nuclear receptor interacting protein 1 abolished the stimulatory effect of miR-193b on adiponectin secretion.
  
  
  CONCLUSIONS
  In human adipocytes, miR-193b controls adiponectin production via pathways involving nuclear transcription factor Yα and possibly nuclear receptor interacting protein 1.
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Belarbi
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Agné
authors.initials: A
authors.lastname: Kulyté
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D023081:CCAAT-Binding Factor / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D000078723:Nuclear Receptor Interacting Protein 1; D009765:Obesity / Q000235:genetics / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D023081:CCAAT-Binding Factor; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; C492061:NFYA protein, human; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1