NMR and cDNA array analysis prior to heart failure reveals an increase of unsaturated lipids, a glutamine/glutamate...

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Metabolomics

Background:

• Obesity is a known risk factor for heart failure.
• The molecular mechanisms linking obesity to heart failure are not fully understood.
• Leptin signaling plays a role in regulating body weight and metabolism.

Purpose of the Study:

• To investigate the kinetic cardiac transcriptome and metabolome in obese Spontaneous Hypertensive Heart Failure (SHHF) rats lacking functional leptin signaling.
• To identify molecular patterns that precede heart failure in this obese rat model.

Main Methods:

• Utilized rat pangenomic high-density macroarrays to analyze left ventricle cardiac gene expression in lean and obese SHHF rats at 4 and 10 months of age.
• Employed 1H NMR spectroscopy to analyze the cardiac metabolome, focusing on metabolite and lipid concentrations.
• Compared gene expression and metabolite profiles between lean and obese rats at different ages.

Main Results:

• Obese rats exhibited distinct gene expression patterns compared to lean rats, with 293 differentially expressed genes in obese hearts versus 222 in lean hearts.
• Cardiac metabolome analysis revealed a global decrease in metabolites (except taurine) and lipids in obese hearts, potentially due to altered gene expression and increased extracellular mass.
• The glutamine to glutamate ratio was significantly lower in obese rats.
• Increased lipid unsaturation and higher omega-3 lipid concentration were observed in the hearts of 10-month-old obese rats.

Conclusions:

• Specific kinetic molecular alterations in cardiac gene expression and lipid metabolism precede heart failure in obese rats with deficient leptin signaling.
• These findings highlight the complex molecular adaptations in the obese heart that contribute to the development of heart failure.