Abstract
β3-Adrenergic receptors (β3-AR) play an important role in the thermogenesis in brown adipose tissue and lipolysis in white adipose tissue. β3-AR agonists developed in the early stages produced marked weight reduction and an anti-diabetic effect in rats and mice, but did not in humans, because of the difference in the chemical structure of the β3-AR. In 1995, a naturally occurring variant (Trp64Arg) of the human β3-AR gene was shown to be correlated with obesity and insulin resistance in Pima Indians. Moreover, the fact that white adipocytes produce various hormones and cytokines that cause life-style-related disease was recently made clear. Because the reduction of the visceral fat is throught to be important to prevent these diseases, the expectations for the human β3-AR agonist having a novel anti-obesity effect are rising. Some interesting findings were recently reported with β3-AR agonists: the difference of the lipolysis was dependent on the existence of the Trp64Arg mutation and the up-regulation effect of the UCP1 and β3-ARs themselves in the adipose tissue and skeletal muscle. Therefore, we introduce informations (past, present and future) on β3-AR agonists in this paper.
