Aim /introduction: Obesity is considered an important risk factor for many metabolic disorders, especially type 2 diabetes mellitus (T2DM), and microRNAs (miRNAs) play a vital role in the development of T2DM. Therefore, we conducted this study to investigate the role of miR-4431 in obesity-associated pathobiology of T2DM.

Materials and methods: Subjects were divided into normal control (n=36), obese (n=36) and T2DM (n=12) groups, and serum miR-4431 levels were analyzed. Adenovirus-vectored miR-4431 mimic or sponge was intraperitoneally injected into normal diet group and high-fat diet group (HFD) mice to investigate glucose tolerance, insulin sensitivity, and lipid levels. The downstream target genes of miR-4431 were predicted using bioinformatics, and they were verified in vitro.

Results: Serum miR-4431 levels were significantly high in obese and T2DM individuals, and it was positively correlated with the body mass index and fasting plasma glucose levels. In HFD mice, miR-4431 levels in the serum, white adipose tissue, and liver were significantly increased. Moreover, miR-4431 impaired glucose tolerance, insulin sensitivity, and lipid metabolism in mice. Bioinformatic prediction suggested that TRIP10 and PRKD1 could be the downstream target genes of miR-4431. HFD mice showed a remarkable reduction in the mRNA levels of TRIP10 and PRKD1 in the liver, which were countered by blocking miR-4431. In HepG2 and L02 cells, miR-4431 could downregulate TRIP10 and PRKD1 while blocking glucose uptake. The luciferase reporter assay showed that miR-4431 could bind TRIP10 and PRKD1 3'-UTR.

Conclusion: miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.

Keywords: PRKD1; T2DM; TRIP10; miR-4431; obesity.