ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Extracellular vesicle miR-425-5p promotes visceral fat reduction via DACT1 suppression in SGLT2i-treated diabetes
Provisionally accepted
Jae-Hyung Park1
Nhi Thi Nguyen1Hye Min Shim1Yun-Ui Bae1Gyeong Im Yu1Junho Kang2Eun Yeong Ha3
Hochan Cho3*- 1Department of Physiology, Keimyung University School of Medicine, Dalseo-gu, Republic of Korea
- 2Department of Research, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea
- 33Department of Internal Medicine, Keimyung University School of Medicine, Dalseo-gu, Republic of Korea
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Objective: In type 2 diabetes (T2D), plasma-derived extracellular vesicle (EV)-microRNAs (miRNAs) contribute to insulin resistance and β-cell dysfunction. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower blood glucose by promoting urinary glucose excretion and are associated with weight loss, although the underlying mechanisms remain unclear. Methods: This study was conducted in two phases. In the screening phase, plasma-derived EV miRNA profiles were analyzed by small RNA sequencing in 13 patients with newly diagnosed, treatment-naive T2D at baseline and after 12 months of SGLT2i therapy. In the validation phase, expression of selected miRNAs was quantified by real-time PCR in an independent cohort of 30 patients at baseline and after 6 and 12 months of treatment. The functional roles of candidate miRNAs were examined in 3T3-L1 adipocytes. Results: Small RNA sequencing identified 18 plasma-derived EV miRNAs exhibiting >1.5-fold expression changes after 12 months of SGLT2i therapy. Quantitative PCR confirmed that five EV miRNAs were significantly upregulated post-treatment. Among these, miR-425-5p showed a strong inverse correlation with waist circumference and visceral fat area. Functional assays in 3T3-L1 adipocytes demonstrated that miR-425-5p suppressed adipogenic differentiation and lipid accumulation by downregulating DACT1, one of its predicted target genes, and reducing DACT1-reporter activity. Conclusion: Plasma-derived EV miR-425-5p, increased by long-term SGLT2i therapy in T2D patients, may inhibit adipocyte differentiation and lipogenesis via DACT1 suppression. These findings suggest a possible mechanistic link through which SGLT2i treatment may ameliorate visceral obesity.
Keywords: Extracellular vesicle, microRNA, Sodium-glucose transporter 2 inhibitor, Type 2diabetes, Obesity, Adipocyte, miR-425-5p, dact1
Received: 15 Oct 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Park, Nguyen, Shim, Bae, Yu, Kang, Ha and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hochan Cho
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