Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 330-090, Korea.
Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 330-090, Korea.
Biofactors. 2018 Mar;44(2):168-179. doi: 10.1002/biof.1392. Epub 2017 Oct 24.
Obesity poses a substantial threat of a worldwide epidemic and requires better understanding of adipose-tissue biology as well as necessitates research into the etiology and therapeutic interventions. In this study, Medicarpin (Med), a natural pterocarpan, was selected (by screening) as a small-molecule inducer of adipocyte differentiation among 854 candidates by using C3H10T1/2 mesenchymal stem cell; a cellular model of adipogenesis. Med induced the expression of brown-adipocyte commitment marker Bmp7 as well as the early regulators of brown fat fate Pparγ, Prdm16, and Pgc-1α during differentiation of C3H10T1/2 mesenchymal stem cells. Med also induced the expression of a key thermogenic marker-uncoupling protein 1 (UCP1)-along with expression of other brown-fat-specific markers and beige-fat-specific markers. Of note, Med significantly reduced the expression of white fat markers too. Furthermore, Med treatment promoted formation of multilocular lipid droplets (LDs), expression of mitochondrial-biogenesis-related genes, and increased oxygen consumption. Gene silencing study revealed that Med promotes the development of brown- and beige-adipocyte characteristics in C3H10T1/2 mesenchymal stem cells through activation of the AMPK pathway, and our data allow us to propose Med as a candidate for therapeutics against obesity or related metabolic disorders. © 2017 BioFactors, 44(2):168-179, 2018.
肥胖症构成了全球流行疾病的巨大威胁，需要更好地了解脂肪组织生物学，并需要研究病因和治疗干预措施。在这项研究中，从 854 种候选药物中，通过 C3H10T1/2 间充质干细胞（脂肪生成的细胞模型）筛选出天然紫檀烷素 Medicarpin（Med）作为脂肪细胞分化的小分子诱导剂。Med 在 C3H10T1/2 间充质干细胞分化过程中诱导棕色脂肪细胞分化标志物 Bmp7 以及棕色脂肪命运早期调节因子 Pparγ、Prdm16 和 Pgc-1α 的表达。Med 还诱导了关键的产热标志物解偶联蛋白 1（UCP1）以及其他棕色脂肪特异性标志物和米色脂肪特异性标志物的表达。值得注意的是，Med 还显著降低了白色脂肪标志物的表达。此外，Med 处理促进了多泡脂滴（LDs）的形成、线粒体生物发生相关基因的表达和耗氧量的增加。基因沉默研究表明，Med 通过激活 AMPK 通路促进 C3H10T1/2 间充质干细胞中棕色和米色脂肪细胞特征的发育，我们的数据允许我们提出 Med 作为治疗肥胖症或相关代谢紊乱的候选药物。©2017 BioFactors，44（2）：168-179，2018。
