Adiponectin-secretion promoting compounds during adipogenesis in human mesenchymal stem cells as peroxisome proliferator-activated receptor modulators

Abstract

Adiponectin, an adipocyte-derived cytokine, plays important roles in the regulation of inflammation, apoptosis, and metabolism. Adiponectin has therapeutic potentials to improve pathologic symptoms of various metabolic diseases like type 2 diabetes, obesity, and microvascular complication. The adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs) has been applied to screen novel adiponectin-secretion promoting compounds. Here, we focused on discovering potential compounds that promote adiponectin secretion in human bone marrow mesenchymal stem cells (hBM-MSCs) by regulating adipocyte differentiation. We performed screening system to identify candidates from natural plant extracts and synthetic compounds. As results, we found that magnolol, honokiol, and methylhonokiol, major chemical components of Magnolia officinalis ethanol extracts promoted adipogenesis and increased adiponectin production in hBM-MSCs. Furthermore, new synthetic benzoimidazol derivatives were also identified to regulate adiponectin secretion effectively. Through molecular target identification research, we discovered that Magnolol, Honokiol, Methylhonokiol enhanced glucose and lipid metabolism by activating both Peroxisome proliferator-activated receptor alpha (PPARα) and PPARγ. Moreover, adiponectin-secretion promoting activity of benzoimidazol derivatives directly associated with PPARγ by high binding affinity. Based on different substituents, three of these derivatives, which the substituents of benzoimidazole were displaced to phenlycarbamolyl showed PPAR partial agonism effect, while others showed PPAR full agonism effect. In our study, we found various adiponectin-secretion promoting compounds as PPAR modulators which could be potential candidates in type 2 diabetes and related metabolic disorders therapy.