Systemic Metabolic Rewiring in a Mouse Model of Left Ventricular Hypertrophy

Area of Science:

• Cardiovascular Biology
• Metabolic Regulation
• Molecular Cardiology

Background:

• Left ventricular hypertrophy (LVH) is linked to poor cardiac outcomes, with metabolism playing a key role.
• LVH hearts shift from fatty acid oxidation (FAO) to glucose metabolism.
• Systemic metabolic changes in LVH are not fully understood.

Purpose of the Study:

• Investigate the impact of LVH on whole-body and cardiac metabolism.
• Determine the role of systemic energy balance and lipid profiles in LVH.
• Assess the therapeutic potential of long-chain fatty acid (LCFA) supplementation.

Main Methods:

• Utilized a mouse model with LVH due to Mybpc3 gene loss.
• Measured whole-body and cellular respiration.
• Analyzed lipid and glycogen stores, and mitochondrial function.

Main Results:

• Mybpc3 deficiency caused adipose tissue depletion, impaired skeletal muscle mitochondrial function, and increased cardiac/hepatic lipid accumulation.
• LVH led to a loss of whole-body metabolic flux.
• LCFA supplementation improved cardiac mitochondrial function and reduced cardiac lipid buildup, but did not fully reverse LVH or systemic metabolic issues.

Conclusions:

• LVH induces significant systemic metabolic rewiring.
• Exogenous LCFA supplementation enhances mitochondrial function in cardiac and skeletal muscle in LVH.
• Targeting systemic metabolism may be crucial for managing LVH complications.