A pivotal role of AMPK signaling in medicarpin-mediated formation of brown and beige.

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.