D-Mannose Inhibits Adipogenic Differentiation of Adipose Tissue-Derived Stem Cells via the miR669b/MAPK Pathway

Abstract

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.

L-Fucose Suppresses Lipid Accumulation via the AMPK Pathway in 3T3-L1 Adipocytes

“…In the present study, treatment with >10 mM Fuc concentrations enhanced the phosphorylation of AMPK and ACC, suggesting that the activation of the AMPK pathway inhibits lipid accumulation. On the other hand, Oil Red O staining results showed that >5 mM Fuc concentrations inhibited lipid accumulation, which is inconsistent with reports regarding its effects on AMPK and ACC; some studies have shown that mannose activates AMPK in Saos-2 cells and suppresses adipocyte differentiation by inhibiting the mitogen-activated protein kinase (MAPK) pathway [ 28 , 29 ]. Thus, Fuc may reduce lipid accumulation via different pathways.…”

Integrated analysis of microRNAs, circular RNAs, long non-coding RNAs, and mRNAs revealed competing endogenous RNA networks involved in brown adipose tissue whitening in rabbits

“…Except for the loss of thermogenic phenotype, lipid accumulation is another obvious characteristic of BAT whitening. The target genes of D0-selective miRNAs were significantly enriched in adipose development-related signal pathways, such as the Ras signaling pathway [ 59 ], MAPK signaling pathway [ 60 ], and PI3K-Akt signaling pathway [ 61 ], which suggested that the disinhibition of the target genes of D0-selective miRNAs in these signal pathways might promote adipogenesis during BAT whitening. The target genes of Y2-selective miRNAs were significantly enriched in cell proliferation-related biological processes, which might suggest that high expression of Y2-selective miRNAs could repress the adipocyte proliferation of BAT in old rabbits.…”

“…Y2-selective circRNAs were predicted to regulate the large number of mRNA via interacting with miRNAs. The adipose development-related signal pathway MAPK [ 60 ] singling pathway were significantly enriched by the Y2-selective circRNAs, which suggested that circRNAs might regulate final stage of BAT whitening via the MAPK signaling pathway by ceRNA mechanism.…”

“…Our data showed that the Y2-selective lncRNA-related ceRNA network was significantly enriched in the Ras signaling pathway. Additionally, previous study revealed that Ras [ 79 ] is an upstream activation protein of PI3K and MAPK and both of PI3K [ 60 ] and MAPK [ 61 ] were key proteins involved in adipogenesis. The enrichment of Ras signaling pathway indicated that lncRNAs might activate genes in Ras signaling pathway and indirectly activate PI3K and MAPK to regulate the final formation of the WAT-like phenotype of BAT by the ceRNA mechanism.…”