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

Abstract

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 2.4 mg/kg/day for 14 days 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 Ser(9) 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.

• Authors: Yuya Fujishima, Norikazu Maeda, Keisuke Matsuda, Noriyuki Komura, Ayumu Hirata, Takuya Mori, Ryohei Sekimoto, Yu Tsushima, Hitoshi Nishizawa, Tohru Funahashi, Iichiro Shimomura
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 444 Issue 2 Pg. 224-9 (Feb 07 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24462873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Adiponectin
• Collagen Type I
• Collagen Type III
• beta Catenin
• Angiotensin II
• mTOR protein, mouse
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Glycogen Synthase Kinase 3

Topics

• Adenoviridae (genetics)
• Adiponectin (genetics, metabolism)
• Angiotensin II (administration & dosage)
• Animals
• Cardiomegaly (chemically induced, genetics, metabolism)
• Collagen Type I (genetics, metabolism)
• Collagen Type III (genetics, 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)
• beta Catenin (metabolism)