Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes

Area of Science:

• Cardiovascular physiology
• Animal models of disease
• Exercise physiology

Background:

• Assessing cardiovascular fitness (CVF) in mice is crucial for understanding disease and testing therapeutics.
• Existing mouse treadmill tests (PXT) lack the sensitivity and comprehensive cardio-metabolic parameters of human GXTs.
• There is a need for a translatable mouse exercise test to assess CVF and cardio-metabolic phenotype.

Purpose of the Study:

• To develop and validate a mouse graded maximal exercise test (GXT) that incorporates staged increases in intensity, mirroring human GXT protocols.
• To enhance the sensitivity of mouse exercise testing for identifying key cardio-metabolic parameters.
• To establish a functional assessment for evaluating CVF in both healthy and diseased mouse models.

Main Methods:

• Developed a mouse-GXT with staged increases in speed and inclination, adapted from human GXT protocols and considering mouse physiology.
• Compared the mouse-GXT against traditional PXTs in healthy mice (C57BL/6J, FVBN/J).
• Assessed the ability of both tests to identify cardio-metabolic parameters (VO2max, anaerobic threshold, metabolic crossover) in healthy and dysfunctional mouse models (diet-induced obesity, Casq2-/-).

Main Results:

• Both mouse-GXT and PXT provided reproducible performance data and measured VO2max.
• Only the mouse-GXT reliably identified the anaerobic threshold and metabolic crossover.
• The mouse-GXT successfully detected impaired CVF in established models of cardiovascular dysfunction.

Conclusions:

• The developed mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice.
• This mouse-GXT provides translatable cardio-metabolic parameters, improving upon existing methods.
• The mouse-GXT is valuable for characterizing the cardio-metabolic phenotype of animal models and evaluating novel therapeutics.