Endocrine Abstracts

Glucosamine (GlcN) is a common supplement that is widely used to improve osteoarthritis, but it would impair myogensis through endoplasmic reticulum (ER) stress eIF2α-ATF4 pathway. Fibroblast growth factor 21 (FGF21) is one of muscle-secreted cytokine that participates in the myogenic differentiation. The Akt-mTOR-p70S6K axis play a pivotal role in protein synthesis, while sustained activation in mTOR signaling that triggers ER stress and conducts FGF21 production in skeletal muscle. However, a relationship between GlcN and muscular FGF21 expression has not been established. The aim of this study was to determine whether GlcN induces FGF21 production in skeletal muscle cells, which could be involved in the activation of Akt-mTOR-p70S6K pathway and ER stress response. We found markedly increased levels of ATF4 and FGF21 in the soleus muscle from chronic GlcN-infused mice. In in vitro studies, treatment of GlcN stimulated FGF21 expression in C2C12 myoblasts. Treatment of cells with FGF receptor inhibitor significantly blocked myogenic differentiation. In addition, ER stress inhibitors reduced GlcN-induced FGF21 expression. Furthermore, inhibition of Akt-mTOR-p70S6K axis prevented the induction of GlcN in eIF2α-ATF4 signaling, resulting suppressed the GlcN-induced FGF21 up-expression. Together, our findings suggest that increased FGF21 levels could induce by the activation of Akt-mTOR-p70S6K signaling pathway and ER stress response, and may be involved in protecting from the GlcN-impaired myogenesis.