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

Biochem Biophys Res Commun. 2014 Feb 7;444(2):224-9. doi: 10.1016/j.bbrc.2014.01.043. Epub 2014 Jan 22.

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.

Keywords: Adiponectin; Angiotensin II; Cardiac hypertrophy; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Angiotensin II / administration & dosage
  • Animals
  • 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
  • beta Catenin / metabolism*

Substances

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