Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance...

Area of Science:

• Skeletal Muscle Physiology
• Pharmacology
• Metabolism

Background:

• Emerging evidence suggests rapamycin (mTOR inhibitor) may mimic caloric restriction (CR) for skeletal muscle health.
• Rapamycin administration (RAP) reduces appetite, but its effects on skeletal muscle differ from CR.
• Understanding these differences is crucial for potential therapeutic applications.

Purpose of the Study:

• To investigate the physiological and molecular differences between RAP and CR in young adult rat skeletal muscle.
• To compare the effects of RAP and paired-feeding (PF) on muscle mass, myofiber size, and contractile function.
• To examine the impact of RAP on mTORC1 signaling, glucose tolerance, and related gene expression.

Main Methods:

• Four weeks of RAP administration or PF in young adult rats.
• Analysis of fast-glycolytic and slow-oxidative muscle characteristics.
• Assessment of plantar flexor muscle contractile function.
• Measurement of mTORC1 signaling, systemic glucose tolerance, and skeletal muscle gene expression (Rictor, hexokinase).

Main Results:

• RAP reduced fast-glycolytic muscle mass and myofiber size, independent of energy intake.
• PF improved plantar flexor muscle function, while RAP did not.
• RAP showed a greater suppression of mTORC1 signaling in slow-oxidative compared to fast-glycolytic muscles.
• RAP exacerbated systemic glucose intolerance and reduced Rictor and hexokinase expression in skeletal muscle.

Conclusions:

• Rapamycin administration has a distinct and potentially negative impact on young adult skeletal muscle compared to caloric restriction.
• RAP negatively affects muscle mass, fiber size, and contractile function, while also impairing glucose metabolism.
• These findings highlight significant differences between rapamycin and CR in skeletal muscle physiology and metabolism.