فهرست نشریات علمی دسترسی آزاد ایران

Objective: The study aims to investigate the regulatory mechanism of the Fndc5 gene in subcutaneous adipose tissueof 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 diabetesrelatedmetabolic changes. By exploring these molecular pathways, the research seeks to enhance our understandingof 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 dividedinto 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 withFndc5 mRNA. RNA and proteins extracted from adipose tissue analyzed by using quantitative real-time polymerasechain reaction (PCR) and immunoblotting, respectively. The dual luciferase reporter assay investigated direct interactionbetween 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, andfasting blood glucose (FBS) were observed. Furthermore, miR-129-5p was identified as a potential regulator of theFndc5 gene, displaying elevated expression in diabetic adipose tissue. Plasmid construction confirmed the binding siteof 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-relatedmetabolic dysregulation.Conclusion: The upregulation of mir-129-5p in these tissues and the subsequent decrease in the expression of theFndc5 gene may play a role in developing pathological conditions in this tissue. These findings highlight potentialmechanisms linking diet-induced diabetes with Fndc5 regulation through miR-129-5p.