Absence of 4-1BB reduces obesity-induced atrophic response in skeletal muscle

Area of Science:

• Muscle Biology
• Metabolic Diseases
• Immunology

Background:

• Obesity triggers skeletal muscle atrophy and metabolic dysfunction, linked to inflammation.
• 4-1BB (tumor necrosis factor receptor superfamily member) was previously implicated in obesity-related muscle inflammation.

Purpose of the Study:

• To investigate the role of 4-1BB in obesity-induced skeletal muscle atrophy and metabolic changes.
• To determine if targeting 4-1BB can ameliorate these effects.

Main Methods:

• Utilized obese mice fed a high-fat diet.
• Assessed the impact of 4-1BB absence on skeletal muscle atrophic factors (MuRF1, Atrogin-1) and NF-κB activity.
• Analyzed changes in mitochondrial oxidative metabolic genes/proteins (e.g., PGC-1α, CPT1β) and oxidative muscle fiber markers.

Main Results:

• Absence of 4-1BB decreased expression of atrophic factors (MuRF1, Atrogin-1) in skeletal muscle.
• NF-κB activity was suppressed in 4-1BB-deficient obese mice.
• Mitochondrial oxidative metabolic gene/protein expression and oxidative muscle fiber markers were increased.

Conclusions:

• 4-1BB-mediated inflammatory signaling contributes to obesity-related skeletal muscle atrophy and metabolic derangement.
• Targeting 4-1BB may offer a therapeutic strategy for combating muscle atrophy and metabolic complications in obesity.