ADCY3 and obesity due to melanocortin 4 receptor deficiency: Later on, Nordman et al. conducted the first genetic association study in Swedish population and demonstrated that the AC3 genetic polymorphisms are not associated with T2D but confer a protective effect in obesity.14 The genetic association study was replicated in Chinese and European populations and the data are consistent.15, 16 In further support, Wang et al. have demonstrated that AC3 knockout mice develop obesity when aging.17 In the present study, we developed obese and diabesity mice by inducement with high-fat diet from C57BL/6 J and db/db mice, respectively.