期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 312, 期 6, 页码 E482-E494出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00251.2016
关键词
insulin resistance; white adipose tissue; microribonucleic acid
资金
- Swedish Research Council
- Swedish Diabetes Foundation
- Diabetes Wellness
- Diabetes Program
- Center for Innovative Medicine at Karolinska Institutet Senior Investigator grants at Karolinska Institutet
- Tore Nilsson Foundation
- Foundation for Gamla Tjanarinnor
- Ake Wiberg Foundation
- European Foundation for the Study of Diabetes/Lilly program
- Novo Nordisk Foundation
- European Union/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking [115372]
- Novo Nordisk Fonden [NNF15OC0015894] Funding Source: researchfish
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.
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