P38α MAPK Coordinates Mitochondrial Adaptation to Caloric Surplus in Skeletal Muscle

Area of Science:

• Metabolic regulation
• Mitochondrial function
• Insulin resistance

Background:

• Excessive calorie intake causes mitochondrial overload, metabolic inflexibility, and insulin resistance.
• Skeletal muscle plays a key role in glucose and fat metabolism.

Purpose of the Study:

• To investigate the role of p38α kinase in skeletal muscle adaptation to a high-fat diet (HFD).
• To determine how attenuated p38α activity impacts glucose and fat metabolism and mitochondrial function.

Main Methods:

• Utilized a mouse model with diminished p38α activity (p38α^AF) fed a high-fat diet.
• Assessed weight gain, insulin tolerance, serum insulin levels, and skeletal muscle insulin signaling.
• Analyzed muscle metabolites, mitochondrial morphology, and myotube respiratory capacity.

Main Results:

• p38α^AF mice showed increased weight gain, higher insulin levels, and impaired insulin tolerance.
• Skeletal muscle in p38α^AF mice exhibited defective insulin signaling, reduced glycolysis and β-oxidation, and mitochondrial abnormalities.
• Myotubes from p38α^AF mice had decreased mitochondrial respiratory capacity and altered nutrient oxidation pathways.

Conclusions:

• p38α is crucial for skeletal muscle adaptation to caloric surplus, promoting mitochondrial biogenesis and regulating nutrient oxidation.
• Attenuated p38α activity leads to mitochondrial overload, metabolic inflexibility, and increased insulin resistance.
• Targeting p38α may offer therapeutic strategies for metabolic disorders associated with obesity.