Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women
| Autor: | Annie M. L. Pettersson, Agné Kulyté, Jurga Laurencikiene, Yasmina Belarbi, Peter Arner, Ingrid Dahlman |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Physiology Biopsy Endocrinology Diabetes and Metabolism Cell Type 2 diabetes White adipose tissue Biology Body Mass Index Cohort Studies 03 medical and health sciences 0302 clinical medicine Insulin resistance Physiology (medical) Internal medicine microRNA medicine Humans Obesity 3' Untranslated Regions Pathological Cells Cultured Gene Expression Profiling Lipogenesis Insulin sensitivity Middle Aged medicine.disease Subcutaneous Fat Abdominal Obesity Morbid MicroRNAs 030104 developmental biology Endocrinology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis RNA Female Insulin Resistance |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 312:E482-E494 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00251.2016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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