Stigmasterol Protects Against Dexamethasone-Induced Muscle Atrophy by Modulating the FoxO3-MuRF1/MAFbx Signaling...

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Glucocorticoid therapy, including dexamethasone (Dexa), commonly causes muscle atrophy.
• This atrophy results from increased protein degradation via the ubiquitin-proteasome system and suppressed protein synthesis.
• The role of stigmasterol, a phytosterol, in mitigating glucocorticoid-induced muscle atrophy remains unexplored.

Purpose of the Study:

• To investigate the protective effects of stigmasterol against dexamethasone-induced muscle atrophy.
• To examine stigmasterol's impact on the FoxO3 and mTORC1 signaling pathways in muscle cells and in vivo.

Main Methods:

• In vitro: C2C12 myotubes treated with dexamethasone ± stigmasterol; assessed morphology, viability, and signaling proteins.
• In vivo: C57BL/6 mice treated with dexamethasone ± stigmasterol; measured body/muscle mass, bone mineral density (BMD), fiber cross-sectional area (CSA), and muscle protein expression.

Main Results:

• Stigmasterol (10 µM) protected myotubes from dexamethasone-induced atrophy, suppressing catabolic (FoxO3/MuRF1/MAFbx) and preserving anabolic (mTOR/p70S6K/4E-BP1) pathways.
• In vivo, stigmasterol mitigated dexamethasone-induced losses in body weight, muscle mass, BMD, and fiber CSA.
• Protection in vivo was linked to reduced upregulation of FoxO3 and MAFbx proteins in muscle tissue.

Conclusions:

• Stigmasterol demonstrates protective effects against dexamethasone-induced muscle atrophy in both cell culture and animal models.
• The mechanism involves modulating the FoxO3-MAFbx catabolic pathway, inhibiting excessive muscle protein breakdown.
• Stigmasterol shows potential as a therapeutic agent for glucocorticoid myopathy.