Cheng Yu, Ferdousi Farhana, Foronda Bryan Angelo, Linh Tran Ngoc, Ganbold Munkhzul, Yada Akira, Arimura Takashi, Isoda Hiroko
Tsukuba Life Science Innovation Program (T-LSI), Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Japan.
Institute of Life and Environmental Sciences, University of Tsukuba, Japan.
Heliyon. 2024 Mar 2;10(5):e26867. doi: 10.1016/j.heliyon.2024.e26867. eCollection 2024 Mar 15.
Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.
角鲨烯（SQ）是一种具有抗炎、抗癌和抗氧化作用的天然化合物，但由于其溶解度低，其生物学特性一直被大大低估。本研究旨在通过全基因组转录组学分析，利用DNA微阵列检测经SQ及其乙二醇（EG）衍生物处理的3T3-L1细胞分化的脂肪细胞的mRNA表达谱，探索四种新合成的SQ两亲性乙二醇（EG）衍生物的基因表达模式差异。转录数据的富集分析表明，与SQ相比，其EG衍生物在大多数情况下产生了不同的、理想的生物学反应。EG衍生物显示出线粒体功能、脂质和葡萄糖代谢以及炎症反应的富集增加。单、二和四SQ显示出细胞成分核糖体的更高富集。组织学染色显示EG衍生物可防止脂质过度积累。此外，线粒体转录因子在经四SQ处理的细胞中上调。值得注意的是，EG衍生物显示出更好的抗炎作用。此外，基因-疾病关联分析预测SQ衍生物在代谢疾病中的生物活性将有显著改善。聚类分析显示，二和四SQ比其他SQ具有更多的功能相似性，这在它们的扫描电子显微镜图像中得到了体现；二和四SQ都自组装成大小和形状相似的囊泡，随后提高了它们的阳离子结合活性。蛋白质-蛋白质相互作用网络进一步揭示，阳离子结合活性可能解释了功能分析中观察到的大部分（如果不是全部）差异。总之，添加EG衍生物可能会改善SQ的生物学反应，从而增强其促进健康的潜力。
