BCL6 coordinates muscle mass homeostasis with nutritional states.

Summary

Using muscle-specific genetic loss- and gain-of-function models, the authors show that BCL6 sustains GH anabolic action by repressing SOCS2, thereby preserving muscle mass and strength. GH in turn suppresses BCL6 via JAK/STAT5, forming a feedback loop linking nutritional state, GH signaling, and muscle mass.

Key Findings

• Muscle-specific BCL6 deletion at perinatal or adult stages markedly reduces muscle mass and strength.
• Viral overexpression of BCL6 in muscle reverses loss of mass and strength.
• BCL6 transcriptionally represses SOCS2, sustaining anabolic GH actions in muscle.
• GH suppresses BCL6 via JAK/STAT5, establishing a feedback loop coordinating nutritional state and muscle mass.

Clinical Implications

Targeting the BCL6–SOCS2 pathway could offer a strategy to enhance GH signaling and preserve muscle mass in conditions such as sarcopenia, cachexia, or GH resistance, pending human validation.

Limitations

• Findings are based on murine models; human validation is lacking.
• Therapeutic translatability and safety of modulating BCL6 in muscle remain untested in clinical settings.

Future Directions

Validate BCL6–SOCS2 regulation of GH signaling in human muscle, assess pharmacologic modulators of this axis, and test efficacy in models of sarcopenia or cachexia.