Tribbles 3 blunts exercise-induced skeletal muscle adaptation

Area of Science:

• Molecular Biology
• Physiology
• Metabolic Research

Background:

• Tribbles 3 (TRB3) is a pseudokinase implicated in disrupting glucose metabolism and inhibiting Akt signaling in obesity and diabetes.
• Previous findings indicated TRB3 overexpression in mouse skeletal muscle reduces muscle mass and function, potentially causing atrophy.

Purpose of the Study:

• To investigate the role of TRB3 in skeletal muscle adaptation to exercise training.
• To determine if TRB3 influences exercise-induced improvements in glucose metabolism and mitochondrial function.

Main Methods:

• Muscle-specific TRB3 transgenic (TG) and wild-type (WT) mice were subjected to voluntary wheel running for 6 weeks.
• Involuntary treadmill exercise was employed to standardize training intensity.
• Glucose tolerance tests were performed.
• Gene expression analysis was conducted for markers of glucose uptake and mitochondrial biogenesis.
• TRB3 knockout (KO) mice were also trained and analyzed.

Main Results:

• TG mice exhibited reduced running distance and impaired glucose tolerance compared to WT littermates.
• TRB3 overexpression suppressed genes essential for glucose uptake and mitochondrial biogenesis, irrespective of training.
• TRB3 KO mice showed improved glucose tolerance independent of training, but without significant changes in key gene markers.

Conclusions:

• TRB3 in skeletal muscle significantly blunts the adaptive benefits of exercise.
• TRB3 negatively impacts exercise-induced improvements in glucose metabolism and potentially mitochondrial function.
• Targeting TRB3 may offer a strategy to enhance skeletal muscle response to exercise.