New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis.
New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis.
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DOI：
10.3389/fcell.2020.577259
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发表时间：
2020
影响因子：
5.5
通讯作者：
Isoda H
中科院分区：
文献类型：
--
作者：
Ganbold M;Ferdousi F;Arimura T;Tominaga K;Isoda H
角鲨烯（Sq）是一种天然化合物，存在于各种植物油、藻类中，深海鲨鱼肝脏中含量更高。它也被称为植物和动物（包括人类）胆固醇合成的中间体。尽管有证据表明其具有抗氧化、抗癌、降血脂、保护肝脏和心脏的作用，但由于其不溶于水的特性，其在细胞功能中的生物学作用可能被低估。为了克服这种疏水性，我们合成了新的两亲性Sq衍生物（HH-Sq）。另一方面，脂肪源性干细胞（ASCs）是再生医学的一个有价值的来源，因为它易于获得和多谱系分化潜力。然而，糖尿病供体来源的ASCs的细胞功能受损仍存在争议。在这项研究中，我们探讨了与Sq相比，HH-Sq对从2型糖尿病受试者获得的ASC的脂肪细胞分化的影响。基因表达谱芯片分析显示，在14天的成脂分化HH-Sq诱导更多的基因参与细胞内信号转导过程，而Sq激活更多的跨膜受体途径相关的基因。此外，Sq和HH-Sq下调和上调的基因数量并不重叠，这表明这两种化合物不仅在化学性质上存在差异，而且可能发挥不同的生物学效应。Sq和HH-Sq都通过增强与能量稳态和胰岛素敏感性相关的基因SIRT 1、PRKAA 2和IRS 1来改善脂肪细胞的代谢。有趣的是，Sq显著增加了早期脂肪形成标志物和脂肪形成基因表达，如PPARG、SREBF 1和CEBPA，但不增加HH-Sq。因此，在HH-Sq处理的脂肪细胞中观察到更小和更少的脂滴形成。根据我们的研究结果，我们报告说，Sq和HH-Sq改善脂肪细胞代谢，但只有HH-Sq防止过度脂肪生成，而不废除脂肪细胞分化。HH-Sq的有益效果提供了从天然化合物合成的衍生物在细胞疗法应用中具有治疗潜力的重要性。
Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, SIRT1, PRKAA2, and IRS1. Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as PPARG, SREBF1, and CEBPA, but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies.
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DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Green DR;Galluzzi L;Kroemer G
通讯作者：
Kroemer G
DOI：
10.1038/nri3071
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.2
作者：
Barbagallo, Ignazio;Li Volti, Giovanni;Vanella, Luca
通讯作者：
Vanella, Luca
DOI：
10.1073/pnas.1006962107
发表时间：
2010-07-13
影响因子：
11.1
作者：
Chau, Mary D. L.;Gao, Jiaping;Gromada, Jesper
通讯作者：
Gromada, Jesper
影响因子：
6.1
作者：
He, HP;Cai, YZ;Corke, H
通讯作者：
Corke, H