Could “Brown Adipose Tissue Failure” be a Cause of Metabolic Syndrome ?

Human brown adipose tissue (BAT) is recognized as one of the most important target tissues in the drug discovery for the treatment of obesity- related metabolic disorders. It is suggested that the BAT improves glucose metabolism independently of its calorigenic capacity, probably via secreting factors. Although several molecules have been identified as BAT-derived glucose metabolism-improving hormones (i.e. BATkines), the crucial factor(s) remains undiscovered. The difficulty in discovering those crucial BATkines may be attributed to the fact that Rnase1 and a variety of chymotrypsin family peptidases are expressed at relatively high levels in murine BATs, which have been used as a material in BATkine hunting. In this review, we describe a new strategy for discovering novel BATkines by using brown adipocytes (BAs) derived from human pluripotent stem cells. We also discuss the possible mechanism how human BAs are involved in the regulation of glucose metabolism.