The key pathological link between obesity and type 2 diabetes is insulin resistance but the molecular mechanisms are not entirely identified. MicroRNAs (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 nine lean women. MicroRNAs 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'UTR 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 vitrodifferentiated adipocytes and directly or indirectly affected several genes/proteins involved in insulin signaling at transcriptional or post-transcriptional levels. Adipose expression of miR-143-3p and miR-652-3p was positively associated with insulin-stimulated lipogenesis in scWAT independently of BMI. In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independently of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin signaling pathways.
- insulin sensitivity
- insulin resistance
- white adipose tissue
- Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism