MicroRNA Expression Profile in Human Visceral and Subcutaneous Adipose Tissues during Pregnancy: Implications for Metabolic Adaptations to Normal Gestation and Putative Mechanism in Gestational Diabetes

Aim: MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression. In adipose tissue miRNAs regulate adipocytes differentiation, metabolic and endocrine functions. The aim of this study was to compare miRNAs expression profile in visceral (VAT) and subcutaneous (SAT) adipose tissues between pregnant and non-pregnant women.

Methods: miRNA expression profile from paired VAT and abdominal SAT was characterized using NanoString nCounter technology in 3 groups: Non-pregnant (n=4) and pregnant (n=8) women and patients with gestational diabetes mellitus (GDM) requiring insulin treatment (n=6). Bioinformatics was employed to detect differentially expressed miRNAs. Results were validated using qPCR for selected miRNAs and miRNA-regulated genes.

Results: Expression differences were notable in VAT: 4 differentially expressed miRNAs were detected between normal-pregnant women and patients with GDM, 2 between normal-pregnant and non-pregnant women and 14 between GDM and non-pregnant women. In SAT, number of differentially expressed miRNAs among the three groups was 3, 1 and 2, respectively.miR-221-3p, miR-222-3p, miR-21-5p were overexpressed and miR-574-3p was underexpressed in VAT of GDM patients compared to non-pregnant women. miR-551b-3p was underexpressed in VAT of GDM patients compared to normal-pregnant women. qPCR analysis in a larger cohort validated findings for miR-221-3p, miR-222-3p, miR-21-5p and several of their putative genes.

Conclusions: miRNA expression profile of visceral and subcutaneous fat depots reveals pregnancy- and GDM-related distinctive pattern, most notably in VAT. miR-221 and miR-222 have been implicated in adipose tissue oxidative stress, inflammation, lipid and glucose metabolism providing putative mechanisms in the adaptation to normal gestation as well as to GDM.