D-mannose reduces adipogenesis by inhibiting the PI3K/AKT signaling pathway

Abstract

Purpose. To explore the effects and potential mechanisms of D-mannose on adipogenic differentiation of two kinds of representative mesenchymal stem cells (MSCs). Methods. We cultured two kinds of representative MSCs, human adipose tissue-derived stromal cells (hADSCs) as well as human bone marrow mesenchymal stem cells (hBMSCs), with adipogenic-induced medium containing D-mannose or D-fructose as the control. Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to detect whether D-mannose had effects on adipogenic differentiation of MSCs. RNA sequencing (RNA-seq) transcriptomic analysis was further used to explore the potential mechanisms of D-mannose on adipogenic differentiation of MSCs. After that, qRT-PCR and WB were used to verify the results of RNA-seq. Last, we removed bilateral ovaries of female rats to establish an estrogen deficiency obesity model, and gave D-mannose intragastric administration. One month later, the femurs of rats were sliced for oil red O staining, and the inhibitory effect of D-mannose on lipid formation in vivo was studied. Results. Oil red O staining, qRT-PCR and WB in vitro demonstrated that D-mannose inhibited the adipogenic differentiation of both hADSCs and hBMSCs. Oil red O staining of femur sections proved that D-mannose was able to reduce in vivo adipogenesis. The results of RNA-seq transcriptomic analysis revealed that the adipogenesis-inhibition effects of D-mannose were performed by antagonizing the PI3K/AKT signaling pathway. Besides, qRT-PCR and WB further verified the results of RNA-seq. Conclusion. Our study indicated that D-mannose was able to reduce adipogenic differentiation of both hADSCs and hBMSCs by antagonizing the PI3K/AKT signaling pathway. D-mannose is expected to be a safe and effective treatment strategy for obesity.