Unveiling the role of miR-186 in SIRT1 regulation in adipocytes: implications for adipogenesis and inflammation in obesity.

IF 1.6 Q4 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes and Metabolic Disorders Pub Date : 2025-01-08 eCollection Date: 2025-06-01 DOI:10.1007/s40200-024-01525-0

Mahdieh Tamkini, Mitra Nourbakhsh, Monireh Movahedi, Abolfazl Golestani

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引用次数: 0

Abstract

Objectives: MicroRNAs (miRNAs) play a crucial role in the onset and progress of obesity. The inflammation of adipose tissue is deemed causative of the complications associated with obesity. This study delved into the potential mechanisms of miRNA-mediated SIRT1 regulation and inflammatory factors modulation in 3T3-L1 cells.

Methods: 3T3-L1 cells were differentiated into mature and hypertrophied adipocytes and the expression of selected miRNAs was evaluated by real-time PCR. 3T3-L1 cells were transfected with the mimic and inhibitor sequences of miR-186, together with the appropriate controls. Western blot analysis assessed the expression level of SIRT1 protein, and the interaction between miR-186 and SIRT1 was scrutinized through a luciferase reporter gene assay.

Results: Across all the mature and hypertrophied cells, the evaluated miRNAs exhibited a significant increase in expression, highlighting their involvement in fat accumulation at a cellular scale. Notably, miR-186-5p displayed the highest expression in differentiated cells and the hypertrophy model. Induction of miR-186 led to attenuation of SIRT1, while its inhibition by miR-186 inhibitor resulted in upregulation of SIRT1 expression. miR-186 caused a remarkable elevation in the expression of inflammatory genes, including IL-6, IL-1β, TNF-α, and MCP-1, indicating a noticeable pattern of relationship between miR-186-induced SIRT-1 inhibition and inflammation.

Conclusions: miR-186 emerges as a pivotal factor in amplifying inflammatory cytokines and down-regulates SIRT1, an effect that might highlight the involvement of SIRT1 in the inflammatory responses of adipocytes, as well as underscoring the crucial role of miR-186 in this process. These findings present miR-186 as a promising target for addressing health challenges related to obesity.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01525-0.

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揭示miR-186在脂肪细胞SIRT1调控中的作用：肥胖中脂肪形成和炎症的意义。

目的：微小核糖核酸（miRNA）在肥胖症的发生和发展过程中起着至关重要的作用。脂肪组织的炎症被认为是肥胖症相关并发症的诱因。本研究探讨了 miRNA 介导的 SIRT1 调节和炎症因子在 3T3-L1 细胞中调节的潜在机制。用 miR-186 的模拟序列和抑制序列以及适当的对照组转染 3T3-L1 细胞。Western印迹分析评估了SIRT1蛋白的表达水平，并通过荧光素酶报告基因测定仔细研究了miR-186与SIRT1之间的相互作用：结果：在所有成熟细胞和肥大细胞中，被评估的 miRNAs 表达量都有显著增加，这表明它们在细胞尺度上参与了脂肪积累。值得注意的是，miR-186-5p 在分化细胞和肥大模型中的表达量最高。诱导 miR-186 会导致 SIRT1 的衰减，而 miR-186 抑制剂抑制 miR-186 则会导致 SIRT1 的表达上调。miR-186 会导致炎症基因（包括 IL-6、IL-1β、TNF-α 和 MCP-1）的表达显著升高，这表明 miR-186 诱导的 SIRT-1 抑制与炎症之间存在明显的关系模式。结论：miR-186 是放大炎症细胞因子和下调 SIRT1 的关键因素，这一效应可能突出了 SIRT1 在脂肪细胞炎症反应中的参与，并强调了 miR-186 在这一过程中的关键作用。这些研究结果表明，miR-186是应对肥胖症相关健康挑战的一个很有前景的靶点：在线版本包含补充材料，可在 10.1007/s40200-024-01525-0获取。

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来源期刊

Journal of Diabetes and Metabolic Disorders Medicine-Internal Medicine

CiteScore

4.80

自引率

3.60%

发文量

210

期刊介绍： Journal of Diabetes & Metabolic Disorders is a peer reviewed journal which publishes original clinical and translational articles and reviews in the field of endocrinology and provides a forum of debate of the highest quality on these issues. Topics of interest include, but are not limited to, diabetes, lipid disorders, metabolic disorders, osteoporosis, interdisciplinary practices in endocrinology, cardiovascular and metabolic risk, aging research, obesity, traditional medicine, pychosomatic research, behavioral medicine, ethics and evidence-based practices.As of Jan 2018 the journal is published by Springer as a hybrid journal with no article processing charges. All articles published before 2018 are available free of charge on springerlink.Unofficial 2017 2-year Impact Factor: 1.816.