Senamontree Sasithon, Lakthan Thitiporn, Charoenpanich Pornsri, Chanchao Chanpen, Charoenpanich Adisri
Department of Biology, Faculty of Science, Silpakorn University, Nakhon Pathom, Thailand.
Department of Food Technology, Faculty of Engineering and Industrial Technology, Silpakorn University, Nakhon Pathom, Thailand.
PeerJ. 2021 Oct 14;9:e12321. doi: 10.7717/peerj.12321. eCollection 2021.
Controlling cellular functions, including stem cell growth and differentiation, can be the key for the treatment of metabolic disorders, such as type II diabetes mellitus (T2DM). Previously identified as peroxisome proliferator-activated receptor gamma () antagonist, betulinic acid (BA) may have the capability to control stem cell homeostasis, benefiting T2DM treatment. In this study, the effects of BA on osteogenesis and adipogenesis mechanisms of human mesenchymal stem cells (hMSCs) were investigated.
We observed that BA increased hMSC osteogenesis by enhancing the alkaline phosphatase activity, calcium deposition, and mRNA expressions of osteogenic markers, namely, runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, BA decreased hMSC adipogenesis with the decrease in glycerol-3-phosphate dehydrogenase activity, reduced intracellular lipid accumulations, down-regulated CCAAT-enhancer-binding protein alpha, and suppressed post-transcriptional adiponectin and leptin secretion. BA increased the brown adipocyte characteristics with the increase in the ratio of small lipid droplets and glucose uptake. Furthermore, the mRNA expressions of brown adipocyte markers, namely, coactivator one alpha, uncoupling protein 1, and interleukin-6 increased.
Our results uncovered the mechanisms of how BA improved glucose and lipid metabolisms by decreasing white adipogenesis and increasing brown adipogenesis. Altogether, BA may be used for balancing glucose metabolisms without the potential side effects on bone loss or weight gain.
控制细胞功能，包括干细胞的生长和分化，可能是治疗代谢紊乱（如2型糖尿病（T2DM））的关键。桦木酸（BA）先前被鉴定为过氧化物酶体增殖物激活受体γ（）拮抗剂，可能具有控制干细胞稳态的能力，有利于T2DM的治疗。在本研究中，研究了BA对人间充质干细胞（hMSCs）成骨和成脂机制的影响。
我们观察到，BA通过增强碱性磷酸酶活性、钙沉积以及成骨标志物（即 runt相关转录因子2、骨钙素和骨桥蛋白）的mRNA表达来增加hMSC的成骨作用。此外，BA通过降低甘油-3-磷酸脱氢酶活性、减少细胞内脂质积累、下调CCAAT增强子结合蛋白α以及抑制转录后脂联素和瘦素分泌来减少hMSC的成脂作用。BA通过增加小脂滴比例和葡萄糖摄取来增加棕色脂肪细胞特征。此外，棕色脂肪细胞标志物（即辅激活因子1α、解偶联蛋白1和白细胞介素-6）的mRNA表达增加。
我们的结果揭示了BA如何通过减少白色脂肪生成和增加棕色脂肪生成来改善葡萄糖和脂质代谢的机制。总之，BA可用于平衡葡萄糖代谢，而不会对骨质流失或体重增加产生潜在副作用。
