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Mesenchymal stem cells (MSCs) are pluripotent stem cells present in various tissues. Previous studies have shown that maxillary/mandibular bone marrow-derived MSCs (MBMSCs) scarcely differentiate into adipocytes. However, the regulatory molecular mechanisms underlying adipogenic differentiation of MBMSCs remain unknown. We investigated the underlying molecular mechanisms that regulate adipogenic differentiation of MBMSCs. We observed no significant differences in cell surface antigen profiles and stem cell marker gene expression in MBMSCs and iliac bone marrow-derived MSCs (IBMSCs). MBMSCs and IBMSCs displayed similar osteogenic and chondrogenic differentiation potentials, whereas MBMSCs showed significantly lower lipid accumulation, adipocyte marker gene expression, and intracellular glucose uptake than that showed by IBMSCs. Expression of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPδ, early B-cell factor 1 (Ebf-1), and Krüppel-like factor 5 (KLF5), which are transcription factors expressed early in adipogenic differentiation, was suppressed in MBMSCs compared to that in IBMSCs. Peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which play important roles in the terminal differentiation of preadipocytes into mature adipocytes, were increased during adipogenic differentiation in MBMSCs and IBMSCs; however, the expression level of these genes in MBMSCs was lower than that in IBMSCs. Furthermore, the level of zinc finger protein 423 (Zfp423), which is involved in the commitment of undifferentiated MSCs to the adipocyte lineage, was significantly lower in undifferentiated MBMSCs than that in IBMSCs. These data indicate that MBMSCs are negatively regulated in the commitment of undifferentiated MSCs to the adipocyte lineage (preadipocytes) and in terminal differentiation into mature adipocytes. These results may elucidate the site-specific characteristics of MBMSCs.

Purple sweet potato (Ipomoea batatas L.) leaf extract (PSPLE) is known to exhibit various biological effects. However, the anti-adipogenic effects of PSPLE on mesenchymal stem cells (MSCs) remain unknown. In the present study, we investigated the effect of PSPLE on the adipogenic differentiation of human bone marrow MSCs.PSPLE treatment significantly reduced lipid accumulation and triglyceride levels during adipogenic differentiation. PSPLE suppressed the expression of PPARγ and C/EBPα, which are the master transcription factors orchestrating adipogenesis; moreover, it inhibited the expression of adiponectin, adipocyte protein 2 (aP2), and lipoprotein lipase (LPL), which are downstream target genes involved in adipogenic differentiation. Furthermore, PSPLE treatment suppressed glucose transporter 4 expression and intracellular glucose uptake and significantly inhibited the adipogenic differentiation induced factor-stimulated Akt signaling activation. These results indicate that PSPLE suppresses the differentiation of undifferentiated MSCs into adipocyte lineages and inhibits the terminal differentiation from preadipocytes into mature adipocytes. Practical application:The increase in the prevalence of obesity worldwide is a problem today. Obesity is induced by an excessive accumulation of adipocytes and causes obesity-related diseases, such as diabetes, hypertension, and hyperlipidemia. Natural compounds derived from plants and fruits have a variety of biological activities and are expected to exert therapeutic effects against various diseases. This study shows that purple sweet potato (Ipomoea batatas L.) leaf extract (PSPLE) suppresses adipogenesis of bone marrow-derived mesenchymal stem cells. Thus, PSPLE may be a novel functional food for controlling obesity.

Administration of Piper retrofractum extract (PRE) has been reported to alleviate edema, but the mechanism underlying this effect is unknown. Promotion of lymphangiogenesis is known to improve lymphedema, but the effect of PRE on lymphangiogenesis remains unclear. In the present study, we investigated whether PRE and specifically, piperine, the main component of PRE, can induce lymphangiogenesis. Treatments with PRE and piperine significantly promoted the proliferation, migration, and tube formation in human dermal lymphatic microvascular endothelial cells (HDLECs) but had no effect on the expression of lymphangiogenic factors. Furthermore, PRE and piperine significantly promoted the phosphorylation of the AKT and ERK proteins in HDLECs, and pretreatment with AKT and ERK inhibitors significantly attenuated the PRE-and piperine-induced lymphangiogenesis. These results indicate that PRE and piperine promote lymphangiogenesis via an AKT-and ERK-dependent mechanism. Practical applicationsThe lymphatic system plays various roles such as maintaining tissue fluid homeostasis, immune defense, and metabolism. Disruption of the lymphatic system results in insufficient fluid drainage, which causes edema. Currently, there are no effective treatments for lymphedema; therefore, the development of novel treatment strategies is desirable. In this study, we showed that PRE and its main component piperine promote lymphangiogenesis in lymphatic endothelial cells. Therefore, PRE has the potential to be used as a novel functional food for relieving lymphedema.