Adenylate cyclase 3: a new target for anti-obesity drug development

Abstract

Obesity has become epidemic worldwide, and abdominal obesity has a negative im- pact on health. Current treatment options on obesity, however, still remain limited.

It is then of importance to find a new target for anti-obesity drug development based upon recent molecular studies in obesity. Adenylate cyclase 3 (ADCY3) is the third member of adenylyl cyclase family and catalyses the synthesis of cAMP from ATP. Genetic studies with candidate gene and genome-wide association study approaches have demonstrated that ADCY3 genetic polymorphisms are associated

with obesity in European and Chinese populations. Epigenetic studies have indi- cated that increased DNA methylation levels in the ADCY3 gene are involved in

the pathogenesis of obesity. Furthermore, biological analyses with animal models have implicated that ADCY3 dysfunction resulted in increased body weight and

fat mass, while reduction of body weight is partially explained by ADCY3 activa- tion. In this review, we describe genomic and biological features of ADCY3, sum- marize genetic and epigenetic association studies of the ADCY3 gene with obesity

and discuss dysfunction and activation of ADCY3. Based upon all data, we suggest

that ADCY3 is a new target for anti-obesity drug development. Further investiga- tion on the effectiveness of ADCY3 activator and its delivery approach to treat ab- dominal obesity has been taken into our consideration.