Inhibitor of FTO, Rhein, Restrains the Differentiation of Myoblasts and Delays Skeletal Muscle Regeneration.

Simple Summary: N6-methyladenosine (m6A) impacts skeletal muscle development. Rhein, an anti-inflammatory agent, inhibits FTO, a key demethylase in m6A metabolism. Our study found that FTO and ALKBH5 expression rises during skeletal muscle fiber formation, while m6A levels fall. After muscle injury, their expression and m6A levels initially surge and then decline. Rhein's FTO inhibition reduces MyHC and MyoG expression, suppressing myoblast differentiation. In mice, Rhein decreased MyHC expression and muscle fiber area, delaying regeneration. Rhein's ability to enhance m6A modification suggests a new medicinal use for this extract. N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits FTO, a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, FTO and ALKBH5 expression increased while m6A levels decreased. After muscle injury, FTO and ALKBH5 expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of FTO by Rhein reduced MyHC and MyoG expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein's ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract. [ABSTRACT FROM AUTHOR]