高脂肪-高果糖饮食通过 miRNA-103 诱导的 miRNA 生物生成途径诱发棕色脂肪细胞功能障碍

Obesities Pub Date : 2024-05-10 DOI:10.3390/obesities4020010
Nitya Shree, Sunitha Meruvu, Min Hi Park, Mahua Choudhury
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引用次数: 0

摘要

背景:肥胖症是一个严重的公共卫生问题,其发病率在全球范围内以惊人的速度增长。西方饮食通常包括高脂肪或高果糖成分,是导致肥胖的主要因素之一。最新研究结果表明,BAT 在调节全身新陈代谢方面发挥着重要作用。然而,BAT 维持体内平衡的明确机制尚不清楚。研究方法用低脂饮食(LFD)或高脂高果糖饮食(HFHFD)喂养六周大的 C57BL/6 雄性小鼠 4、12 和 20 周。结果我们观察到,在高脂高果糖饮食条件下,小鼠的BAT重量明显增加,同时BAT变白,且呈时间依赖性。与此同时,UCP1和PGC1α蛋白明显减少,Bax/Bcl-2比值早在12周时就明显增加,这表明在HFHFD条件下细胞凋亡增加。有趣的是,在 miRNA 生物发生机制中具有种子序列的 miRNA-103 表达,即 Dicer,在 HFHFD 12 周和 20 周后显著上调。Dicer和另一个生物发生调节因子TRBP2在HFHFD持续4周后表现出明显的上调。相反,这些基因的表达在 HFHFD 12 周和 20 周时明显下调,随后在 12 周时蛋白水平明显下降。为了证实这种机理上的联系,在体外敲除 miRNA-103 会显著上调 Dicer 和 TRBP2 基因。然而,只有 Dicer 在翻译水平上表现出明显的增加。结论总之,我们得出结论:HFHFD 可通过 miRNA-103 抑制 Dicer 而引起 BAT 功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
High-Fat-High-Fructose Diet Elicits Brown Adipocyte Dysfunction through miRNA-103 Induced miRNA Biogenesis Pathway
Background: Obesity is a critical public health concern with its prevalence growing at an alarming rate worldwide. The Western diet that typically includes high-fat or high-fructose components is one of the leading contributing factors of obesity. Recent findings demonstrate the essential role of BAT in regulating whole-body metabolism. However, the explicit mechanism through which BAT maintains homeostasis is still unknown. Methods: Six-week-old C57BL/6 male mice were fed either a low-fat diet (LFD) or a high-fat high-fructose diet (HFHFD) for 4, 12, and 20 weeks. Results: We observed a significant increase in BAT weight under HFHFD along with BAT whitening in a time-dependent manner. This was also accompanied by a significant decrease in UCP1 and PGC1α protein, as well as a significant increase in the Bax/Bcl-2 ratio as early as 12 weeks, indicating increased apoptosis under HFHFD. Interestingly, miRNA-103 expression that holds a seed sequence within the miRNA biogenesis machinery, Dicer, was significantly upregulated after 12 and 20 weeks of HFHFD. Dicer and another biogenesis regulator, TRBP2, exhibited significant upregulation at 4 weeks of HFHFD. Conversely, those gene expressions were significantly downregulated at 12 and 20 weeks of HFHFD, followed by a significant decrease in the protein level at 12 weeks. To confirm the mechanistic connection, miRNA-103 knockdown in vitro significantly upregulated Dicer and the TRBP2 gene. However, only Dicer exhibited a significant increase at the translational level. Conclusion: Overall, we conclude that HFHFD may elicit BAT dysfunction by inhibiting Dicer via miRNA-103.
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