miR-129-5p Modulates Fndc5 Expression in Adipose Tissue of Diabetic Mice.

Abstract

Objective: The study aims to investigate the regulatory mechanism of the Fndc5 gene in subcutaneous adipose tissue of diabetic mice, with a focus on the role of miR-129-5p in the pathogenesis of type 2 diabetes mellitus (T2DM). Specifically, it examines how the dysregulation of miR-129-5p affects Fndc5 expression and contributes to diabetesrelated metabolic changes. By exploring these molecular pathways, the research seeks to enhance our understanding of T2DM and identify potential therapeutic targets for its complications.

Materials and methods: In this experimental study, a total of 12 C57BL/6 male mice (6 weeks old) were divided into control and 60% high-fat enriched advanced glycation end products (60% HF-AGE) groups (n=6 per group). Bioinformatics analysis involved mining altered miRNAs in type 2 diabetes and predicting miRNA interactions with Fndc5 mRNA. RNA and proteins extracted from adipose tissue analyzed by using quantitative real-time polymerase chain reaction (PCR) and immunoblotting, respectively. The dual luciferase reporter assay investigated direct interaction between miR-129-5p and the Fndc5 gene using HEK293T cells transfected with relevant vectors.

Results: In mice receiving a 60% HF-AGE diet, significant increases in energy intake, body weight, insulin levels, and fasting blood glucose (FBS) were observed. Furthermore, miR-129-5p was identified as a potential regulator of the Fndc5 gene, displaying elevated expression in diabetic adipose tissue. Plasmid construction confirmed the binding site of miR-129-5p on the Fndc5 3'UTR, while dual luciferase assays validated its direct targeting of the Fndc5 transcript. This interaction corresponded with a reduced expression of Fndc5, highlighting its potential role in diabetes-related metabolic dysregulation.

Conclusion: The upregulation of mir-129-5p in these tissues and the subsequent decrease in the expression of the Fndc5 gene may play a role in developing pathological conditions in this tissue. These findings highlight potential mechanisms linking diet-induced diabetes with Fndc5 regulation through miR-129-5p.