title: Adenylate cyclase 3: a new target for anti-obesity drug development.
abstract: Obesity has become epidemic worldwide, and abdominal obesity has a negative impact 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 indicated 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 activation. In this review, we describe genomic and biological features of ADCY3, summarize 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 investigation on the effectiveness of ADCY3 activator and its delivery approach to treat abdominal obesity has been taken into our consideration.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.affiliation: Unit for Medical Education, Centre for Learning and Knowledge, Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, 17177, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Seed Ahmed
authors.affiliation: Rolf Luft Center for Diabetes Research and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, 17176, Sweden.
authors.forename: C-G
authors.initials: CG
authors.lastname: Östenson
authors.affiliation: Department of Clinical Science, Intervention and Technologies, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, 14157, Sweden.|Center of Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, 17176, Sweden.
authors.forename: H F
authors.initials: HF
authors.lastname: Gu
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D018390:Gene Targeting; D006801:Humans; D009765:Obesity / Q000235:genetics* / Q000628:therapy*
chemical_list: D019440:Anti-Obesity Agents; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3
keywords: Adenylate cyclase 3; body mass index; obesity