title: Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women.
abstract: The key pathological link between obesity and type 2 diabetes is insulin resistance, but the molecular mechanisms are not entirely identified. micro-RNAs (miRNA) are dysregulated in obesity and may contribute to insulin resistance. Our objective was to detect and functionally investigate miRNAs linked to insulin sensitivity in human subcutaneous white adipose tissue (scWAT). Subjects were selected based on the insulin-stimulated lipogenesis response of subcutaneous adipocytes. Global miRNA profiling was performed in abdominal scWAT of 18 obese insulin-resistance (OIR), 21 obese insulin-sensitive (OIS), and 9 lean women. miRNAs demonstrating differential expression between OIR and OIS women were overexpressed in human in vitro-differentiated adipocytes followed by assessment of lipogenesis and identification of miRNA targets by measuring mRNA/protein expression and 3'-untranslated region analysis. Eleven miRNAs displayed differential expression between OIR and OIS states. Overexpression of miR-143-3p and miR-652-3p increased insulin-stimulated lipogenesis in human in vitro differentiated adipocytes and directly or indirectly affected several genes/proteins involved in insulin signaling at transcriptional or posttranscriptional levels. Adipose expression of miR-143-3p and miR-652-3p was positively associated with insulin-stimulated lipogenesis in scWAT independent of body mass index. In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independent of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin-signaling pathways.
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Belarbi
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Pettersson
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden agne.kulyte@ki.se.
authors.forename: Agné
authors.initials: A
authors.lastname: Kulyté
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D050155:Lipogenesis; D008297:Male; D035683:MicroRNAs / Q000819:agonists / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C542359:MIRN143 microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs; C039919:RNA, recombinant; D012313:RNA
keywords: insulin resistance; microribonucleic acid; white adipose tissue