LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation

Area of Science:

• Cellular biology
• Epigenetics
• Muscle differentiation

Background:

• Cellular metabolic properties are influenced by environmental factors like nutrients and hormones.
• Epigenetic mechanisms are implicated in metabolic programming, but links to chromatin modifiers are unclear.

Purpose of the Study:

• To investigate the role of lysine-specific demethylase-1 (LSD1) in regulating metabolic programs during myogenic differentiation.
• To elucidate the mechanism by which glucocorticoids influence LSD1 activity and subsequent gene expression.

Main Methods:

• Transcriptomic and epigenomic analyses to identify LSD1 targets.
• Cell culture experiments with myoblasts and hormone treatments (dexamethasone).
• Assessment of myotube oxidative capacity and histone methylation patterns.

Main Results:

• LSD1 represses oxidative metabolism and slow-twitch myosin genes during myogenic differentiation.
• Glucocorticoid treatment, specifically dexamethasone (Dex), reduces LSD1 levels via JADE-2-mediated proteasomal degradation.
• LSD1 inhibition combined with Dex treatment enhances oxidative gene expression and H3K4 methylation in differentiating myoblasts.

Conclusions:

• LSD1 acts as a key epigenetic regulator linking glucocorticoid signaling to metabolic reprogramming in muscle cells.
• This mechanism highlights a novel pathway controlling cellular energy metabolism during differentiation.