Intramuscular adipose tissue restricts functional muscle recovery.

With age and disease, skeletal muscle is progressively lost and replaced by fibrotic scar and intramuscular adipose tissue (IMAT). While strongly correlated, it remains unclear whether IMAT has a functional impact on muscle. In the present study, we evaluated the impact of IMAT on muscle regeneration by creating a mouse model where the cellular origin of IMAT, fibro/adipogenic progenitors (FAPs), is prevented from differentiating into adipocytes (mFATBLOCK model). We found that blocking IMAT after an adipogenic injury allowed muscle to regenerate more efficiently, resulting in enhanced functional recovery. Our data explain why acute muscle injuries featuring IMAT infiltration, such as rotator cuff tears and acute denervation injuries, exhibit poor regeneration and lead to a loss of muscle function. It also demonstrates the therapeutic importance of preventing IMAT formation in acute injuries in order to maximize regeneration and minimize loss in muscle mass and function.