Obesity is associated with heart failure and cardiac hypertrophy. Adiponectin has been shown to play a protective role for cardiovascular diseases. The beta-catenin signaling pathway is deeply involved in cardiac hypertrophy. However, the effect of adiponectin on beta-catenin signaling has not been investigated in cardiac hypertrophy. Present study aimed to clarify the involvement of adiponectin and beta-catenin signaling pathway in the mouse model of angiotensin II (AngII)-induced cardiac hypertrophy. In hearts of Wild type (WT) mice, AngII dose-dependently augmented cytosolic beta-catenin protein level. WT and adiponectin knockout (Adipo-KO) mice were administered with AngII at 2.4 mg/kg/day for 14 days and were also injected with adenovirus expressing the adiponectin (Ad-Adipo) or the beta-galactosidase (Ad-beta gal). Cardiac mRNA levels relating to hypertrophy and beta-catenin signaling were increased in Adipo-KO mice and these changes were reversed by Ad-Adipo. Phosphorylation of Akt was increased in Adipo-KO mice and such increases were reversed by Ad-Adipo. Furthermore, the phosphorylation of glycogen synthase kinase 313 (GSK313) at Ser(9) and cytosolic beta-catenin level were increased in Adipo-KO mice and they were significantly reduced by Ad-Adipo treatment. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by Ad-Adipo-mediated adiponectin supplementation in WT and Adipo-KO mice. The current study suggests that adiponectin attenuates AngII-induced cardiac hypertrophic signals partly through Akt/GSK3 beta/beta-catenin and Akt/mTOR pathways. (C) 2014 Elsevier Inc. All rights reserved.