Leptin From Fibro-Adipogenic Progenitor Cells (FAPs) Regulates Masseter Muscle Disuse Atrophy and Ectopic Fat...

Area of Science:

• Muscle physiology and regeneration
• Cellular metabolism and signaling
• Biomarkers of muscle atrophy

Background:

• Disuse atrophy leads to excessive fat accumulation in muscles, impairing function and progression.
• Leptin is a key regulator of skeletal muscle fat metabolism.
• Masticatory muscle atrophy presents aesthetic and functional challenges.

Purpose of the Study:

• To investigate leptin's role and mechanism in masseter muscle disuse atrophy.
• To identify the local source of leptin in the masseter muscle.

Main Methods:

• Established a mouse model of masseter muscle disuse atrophy.
• Administered exogenous leptin and nilotinib (to induce FAP apoptosis).
• Utilized transcriptomic sequencing and in vitro validation.

Main Results:

• Disuse atrophy significantly increased muscle triglycerides and MuRF-1 expression.
• Leptin injection reduced lipid accumulation and atrophy.
• Leptin upregulated peroxisome proliferator-activated receptor α (PPARα), crucial for lipid metabolism.
• Fibro-adipogenic progenitor cells (FAPs) were identified as a local source of leptin.
• Nilotinib-induced FAP apoptosis worsened muscle lipid accumulation and atrophy.

Conclusions:

• Reduced leptin secretion from FAPs in disuse atrophy triggers lipid accumulation, exacerbating muscle degeneration.
• FAPs play a critical role in maintaining masseter muscle homeostasis via leptin-mediated mechanisms.