The adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) plays an important role in the process of obesity and host metabolism. D-Mannose shows a potential regulating function for fat tissue expansion and glucose metabolism. To explore the mechanisms through which D-mannose affects the adipogenic differentiation of adipose-derived stem cells in vitro, we cultured the ADSCs with adipogenic medium inducement containing D-mannose or glucose as the control. The adipogenic differentiation specific markers Pparg and Fabp4 were determined by real-time PCR. The Oil Red O staining was applied to measure the lipid accumulation. To further explore the mechanisms, microarray analysis was performed to detect the differences between glucose-treated ADSCs (G-ADSCs) and D-mannose-treated ADSCs (M-ADSCs) in the gene expression level. The microarray data were further analyzed by a Venn diagram and Gene Set Enrichment Analysis (GSEA). MicroRNA inhibitor transfection was used to confirm the role of key microRNA. Results. D-Mannose intervention significantly inhibited the adipogenic differentiation of ADSCs, compared with the glucose intervention. Microarray showed that D-mannose increased the expression of miR669b, which was an inhibitor of adipogenesis. In addition, GSEA and western blot suggested that D-mannose suppressed the adipogenic differentiation via inhibiting the MAPK pathway and further inhibited the expression of proteins related to glucose metabolism and tumorigenesis. Conclusion. D-Mannose inhibits adipogenic differentiation of ADSCs via the miR669b/MAPK signaling pathway and may be further involved in the regulation of glucose metabolism and the inhibition of tumorigenesis.

中文翻译：

---

D-甘露糖通过miR669b / MAPK途径抑制脂肪组织干细胞的成脂分化

脂肪组织衍生干细胞（ADSCs）的成脂分化在肥胖和宿主代谢过程中起重要作用。D-甘露糖显示出对脂肪组织扩张和葡萄糖代谢的潜在调节功能。为了探索D-甘露糖影响体外脂肪干细胞成脂分化的机制，我们用含D-甘露糖或葡萄糖的成脂培养基诱导培养了ADSC。成脂分化特异性标记物Pparg和Fabp4通过实时PCR确定。油红O染色用于测量脂质积累。为了进一步探索机制，进行了微阵列分析以检测基因表达水平上葡萄糖处理的ADSC（G-ADSCs）和D-甘露糖处理的ADSC（M-ADSCs）之间的差异。通过维恩图和基因集富集分析（GSEA）进一步分析了微阵列数据。MicroRNA抑制剂转染用于确认关键microRNA的作用。结果。与葡萄糖干预相比，D-甘露糖干预显着抑制了ADSC的脂肪形成分化。微阵列显示D-甘露糖增加了miR669b的表达，miR669b是脂肪形成的抑制剂。另外，GSEA和蛋白质印迹表明D-甘露糖通过抑制MAPK途径抑制了脂肪形成分化，并进一步抑制了与葡萄糖代谢和肿瘤发生有关的蛋白质的表达。结论。D-甘露糖通过miR669b / MAPK信号通路抑制ADSC的脂肪形成分化，并且可能进一步参与葡萄糖代谢的调节和肿瘤发生的抑制。