Estrogen Regulates Mitochondrial Activity Through Inducing Brain-Derived Neurotrophic Factor Expression in Skeletal...

Area of Science:

• Endocrinology
• Molecular Biology
• Skeletal Muscle Physiology

Background:

• Estrogen is crucial for reproductive health and influences lipid and glucose metabolism.
• The precise molecular mechanisms of estrogen's metabolic regulation are not fully understood.
• Brain-derived neurotrophic factor (BDNF) is implicated in various cellular functions.

Purpose of the Study:

• To investigate the role of estrogen in regulating BDNF synthesis in skeletal muscle.
• To elucidate the molecular pathways through which estrogen affects skeletal muscle metabolism.
• To determine if BDNF mediates estrogen's effects on mitochondrial activity.

Main Methods:

• Primary myotube cultures and C2C12 myoblast cell lines were used to study BDNF production.
• Ovariectomized mice were utilized to assess the in vivo effects of estrogen depletion and administration.
• Estrogen receptor binding assays and shRNA-mediated gene silencing were employed to explore molecular mechanisms.

Main Results:

• Estradiol (E2) induced dose- and time-dependent BDNF production in cultured myotubes.
• Estrogen depletion reduced Bdnf expression in mouse skeletal muscle, which was reversible by E2.
• Estrogen receptor alpha (ERα) bound to the Bdnf gene promoter, and inhibiting BDNF production impaired E2-induced mitochondrial activation.

Conclusions:

• Estrogen is a significant stimulator of BDNF synthesis in skeletal muscle.
• BDNF acts as an effector of estrogen signaling in regulating skeletal muscle mitochondrial activity.
• Estrogen influences skeletal muscle fuel metabolism, partly through BDNF-mediated pathways.