Effect of adiponectin on cardiac β-catenin signaling pathway under angiotensin II infusion

• Published in: Biochemical and biophysical research communications 2014-02, Vol.444 (2), p.224-229
• Main Authors: Fujishima, Yuya, Maeda, Norikazu, Matsuda, Keisuke, Komura, Noriyuki, Hirata, Ayumu, Mori, Takuya, Sekimoto, Ryohei, Tsushima, Yu, Nishizawa, Hitoshi, Funahashi, Tohru, Shimomura, Iichiro
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Angiotensin II; Angiotensin II - administration & dosage; Animals; beta Catenin - metabolism; Cardiac hypertrophy; Cardiomegaly - chemically induced; Cardiomegaly - genetics; Cardiomegaly - metabolism; Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; Female; Gene Expression - drug effects; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Immunoblotting; Infusion Pumps, Implantable; Mice; Mice, Knockout; Myocardium - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; β-catenin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.01.043

•The effect of adiponectin on β-catenin signaling has not been investigated.•Angiotensin II (AngII)-induced cardiac hypertrophy model was used in this study.•The β-catenin and hypertrophic signals were augmented in adiponectin null mice.•Such increases were reversed by adiponectin treatment.•Adiponectin attenuates AngII-induced cardiac hypertrophic signals. Obesity is associated with heart failure and cardiac hypertrophy. Adiponectin has been shown to play a protective role for cardiovascular diseases. The β-catenin signaling pathway is deeply involved in cardiac hypertrophy. However, the effect of adiponectin on β-catenin signaling has not been investigated in cardiac hypertrophy. Present study aimed to clarify the involvement of adiponectin and β-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 β-catenin protein level. WT and adiponectin knockout (Adipo-KO) mice were administered with AngII at 2.4mg/kg/day for 14days and were also injected with adenovirus expressing the adiponectin (Ad-Adipo) or the β-galactosidase (Ad-βgal). Cardiac mRNA levels relating to hypertrophy and β-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 3β (GSK3β) at Ser9 and cytosolic β-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/GSK3β/β-catenin and Akt/mTOR pathways.