High-Frequency Stimulation on Skeletal Muscle Maintenance in Female Cachectic Mice

Area of Science:

• Exercise Physiology
• Cancer Biology
• Muscle Adaptation

Background:

• Cancer cachexia leads to significant unintentional weight loss, impacting patient survival and treatment response.
• Previous research on cachexia's effects on muscle adaptation has primarily focused on male models, neglecting sex-specific responses.
• Understanding how cancer cachexia affects female muscle adaptation to exercise is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate if high-frequency electric stimulation (HFES) can mitigate muscle mass reduction during cancer cachexia progression in female mice.
• To examine the impact of HFES on muscle fiber characteristics, signaling pathways, and oxidative capacity in female tumor-bearing mice.

Main Methods:

• Female wild-type and tumor-bearing mice underwent single or repeated bouts of HFES targeting the tibialis anterior (TA) muscle.
• Evaluated TA muscle mass, myofiber size (type IIa and IIb), anabolic and catabolic signaling pathways (mTOR, AMPK), and skeletal muscle oxidative capacity.
• Compared responses between tumor-bearing (Min) and healthy (WT) mice.

Main Results:

• Tumor-bearing mice exhibited reduced TA muscle mass and fiber sizes compared to controls.
• HFES significantly increased muscle weight and fiber cross-sectional area in both WT and Min mice.
• HFES enhanced mTOR signaling, boosted myofibrillar protein synthesis, attenuated AMPK activity, and preserved skeletal muscle oxidative capacity.

Conclusions:

• Repeated bouts of HFES can effectively counteract cancer-induced muscle mass loss in female mice.
• HFES activates muscle protein synthesis via mTOR signaling, representing a promising therapeutic approach for managing cancer cachexia in females.