AdipoRon prevents l-thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway

Acta Biochim Biophys Sin (Shanghai). 2019 Jan 1;51(1):20-30. doi: 10.1093/abbs/gmy152.

Abstract

Cardiac hypertrophy is a risk factor which can intrigue heart failure. In the present study, we explored whether AdipoRon attenuates isoprenaline (ISO) or l-thyroxine-induced cardiac hypertrophy in Sprague-Dawley (SD) rats and whether the anti-hypertrophy effect is mediated by AMPK-related pathway. Here, cardiac hypertrophy was induced by injection of l-thyroxine or ISO in SD rats. In the treatment group, AdipoRon was co-administered. We examined the effects of AdipoRon on cardiac hypertrophy and hypertrophy signaling pathway. The weight of SD rats was recorded every day. Rats were killed for collection of blood and heart under anesthesia. The left heart weight and heart weight were weighed. Paraffin-embedded heart tissue regions (4 μm) were stained with hematoxylin and eosin or Masson to detect left heart hypertrophy and myocardial fibrosis. The serum BNP levels were determined by using an enzyme-linked immunosorbent assay. The mRNA levels of ANP, BNP, PGC-1α, and ERRα were evaluated by real-time PCR analysis. The protein expression levels of PGC-1α, ERRα, and pAMPK/AMPK were determined by western blot analysis. The results showed that AdipoRon significantly reversed heart weight (HW)/body weight (BW) ratio, left ventricular (LV)/BW ratio, serum BNP level and the mRNA level of ANP and BNP induced by ISO or l-thyroxine. ISO or l-thyroxine reduced both the mRNA level and protein level of ERRα and PGC-1α, and also reduced the protein level of pAMPK/AMPK. However, AdipoRon reversed ISO or l-thyroxine-induced changes of pAMPK/AMPK, ERRα, and PGC-1α. Our data indicated that the effects of AdipoRon are mediated partly by activating AMPK-related pathway, and AdipoRon plays a potential role in the prevention of cardiac hypertrophy.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Body Weight / drug effects
  • Cardiomegaly / chemically induced
  • Cardiomegaly / metabolism
  • Cardiomegaly / prevention & control*
  • Gene Expression / drug effects
  • Isoproterenol
  • Male
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, Brain / metabolism
  • Organ Size / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Piperidines / pharmacology*
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Thyroxine

Substances

  • AdipoRon
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Piperidines
  • Ppargc1a protein, rat
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • AMP-Activated Protein Kinases
  • Isoproterenol
  • Thyroxine