Intramuscular adipose tissue physically 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 effects of IMAT during muscle injury by creating a mouse model where the cellular origin of IMAT, fibro/adipogenic progenitors (FAPs), are prevented from differentiating into adipocytes (FATBLOCK model). We found that blocking IMAT after an adipogenic injury allowed muscle to regenerate more efficiently, resulting in enhanced function. 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 in 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. Transcriptomic profiling using RNAseq was performed on RNA derived from whole muscle lysate from tibialis anterior muscle 5 days post glycerol injury. Two groups of whole muscle were sequenced, one from wild type muscle, and another from FAPs in which ppary was conditionally deleted. A total of 6 control and 6 FAP-no ppary samples were used.