Astragalus polysaccharide regulates brown adipogenic differentiation through miR-1258-5p-modulated cut-like homeobox 1 expression
Astragalus polysaccharide regulates brown adipogenic differentiation through miR-1258-5p-modulated cut-like homeobox 1 expression
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DOI：
10.1093/abbs/gmab151
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发表时间：
2021-10-30
影响因子：
3.7
通讯作者：
Zhao, Junxing
中科院分区：
文献类型：
--
作者：
Cao, Yuxin;Deng, Buhao;Zhao, Junxing
黄芪多糖（APS）是黄芪的主要天然活性成分，被公认为全球最受欢迎的草药之一。增强棕色脂肪组织的形成和功能会增加能量消耗，因此可能用于对抗肥胖和 2 型糖尿病。本研究的目的是探讨APS对棕色脂肪细胞形成的影响及其机制。对小鼠 C3H10T 1/2 细胞进行 APS，并测定增殖和棕色脂肪形成分化。结果显示，APS表现出增殖能力下降，并伴有增殖细胞核抗原、细胞周期蛋白D1和细胞周期蛋白依赖性激酶4的下调。APS促进C3H10T 1/2细胞向棕色脂肪细胞分化，并诱导关键棕色脂肪形成转录因子的表达，包括CCAAT/增强子结合蛋白β、解偶联蛋白1和含有PR结构域的16。重要的是，APS使胰岛素能够发挥作用棕色脂肪细胞中的致敏作用，可能通过激活经典磷脂酰肌醇-3-激酶 (PI3K)/蛋白激酶 B (AKT) 信号通路和 AMP 激活蛋白激酶 (AMPK) 来进行。此外，剪切样同源盒 1 (CUX1) 的水平与棕色脂肪形成分化呈正相关，而 APS 通过与 miR-1258-5p 相互作用调节 Cux/表达。值得注意的是，APS 对棕色脂肪形成的促进作用被 Cux/敲除消除了。总的来说，我们的结果表明 APS 通过 miR-1258-5p 调节 Cux/ 来增强 C3H10T 1/2 细胞向棕色脂肪细胞的分化。
Astragalus polysaccharide (APS) is the major natural active component of Astragalus membranaceus, which has been recognized as one of the most popular herbal medicines worldwide. Enhancing the formation and function of brown adipose tissue increases energy expenditure and hence may potentially be used against obesity and type 2 diabetes. The aim of the present study was to explore the effect and mechanism of APS on brown adipocyte formation. Mouse C3H10T 1/2 cells were subject to APS, and both proliferation and brown adipogenic differentiation were determined. The results showed that APS exhibits a decreased proliferation ability, which is accompanied by downregulated proliferating cell nuclear antigen, cyclin D1, and cyclin-dependent kinase 4. APS promotes the differentiation of C3H10T 1/2 cells into brown adipocytes and induces the expressions of key brown adipogenic transcriptional factors, including CCAAT/enhancerbinding protein beta, uncoupling protein 1, and PR domain-containing 16. Importantly, APS enables insulin sensitization in brown adipocytes, which may proceed through activation of the canonical phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and AMP-activated protein kinase (AMPK). Furthermore, the level of cut-like homeobox 1 (CUX1) is positively related to brown adipogenic differentiation, while APS regulates Cux/expression through interaction with miR-1258-5p. Notably, the promotional effect of APS on brown adipogenic differentiation was abolished by Cux/knockout. Collectively, our results suggest that APS enhances the differentiation of C3H10T 1/2 cells into brown adipocytes through regulating Cux/via miR-1258-5p.