ZSF1 lean rats - How healthy are they?

Area of Science:

• Cardiology
• Physiology
• Animal Models

Background:

• ZSF1 lean rats are common controls in cardiometabolic studies.
• Lean rats carry mutant leptin receptor alleles, raising concerns about their 'healthy' status.
• Previous studies lack comprehensive physiological comparisons with standard controls.

Purpose of the Study:

• To compare ZSF1 lean rats with Wistar rats across multiple physiological systems.
• To evaluate the suitability of ZSF1 lean rats as healthy controls.
• To identify early signs of cardiometabolic dysfunction in ZSF1 lean rats.

Main Methods:

• Comparison of 32-week-old female ZSF1 lean and Wistar rats.
• Assessment of physiological, myocardial, vascular, skeletal muscle, and mitochondrial parameters.
• Hemodynamic measurements, tissue mass analysis, and functional testing.

Main Results:

• ZSF1 lean rats had lower body weight but increased organ mass (heart, kidney, skeletal muscle).
• Despite thicker ventricular walls, systolic and diastolic function were preserved, yet ventricular stiffness and filling pressures were elevated.
• Reduced smooth muscle responsiveness and increased passive vascular stiffness were observed in ZSF1 lean rats.

Conclusions:

• ZSF1 lean rats display significant physiological differences compared to Wistar rats.
• Early-phase diastolic and vascular stiffness indicate a passive compliance disorder.
• The suitability of ZSF1 lean rats as healthy controls in cardiometabolic research is questionable.