Sesamin, a major
lignin mainly found in sesame (Sesamum indicum) oil and sesame seeds, has been demonstrated to possess lipoclasis-promoting, antiobesity, and
antidiabetic effects. Irisin is a newly discovered
myokine that has attracted great interest as a key target to prevent/treat
obesity and its related
metabolic diseases. However, the effect and potential mechanism of
sesamin on FNDC5/irisin are still vacant. In this study, we showed that
sesamin treatment increased FNDC5/irisin activation and regulated
SIRT1, PGC-1α, and p-SMAD3/SMAD3 expression in C2C12 cells. By using specific inhibitors and lentivirus in C2C12 cells, we found that the
SIRT1/SMAD3 axis plays an important role in
sesamin regulated FNDC5/irisin activation. We also found that
sesamin treatment activated FNDC5 expression and regulated the
SIRT1/SMAD3 signaling axis in mice's skeletal muscle. What is more, by the high-fat diet induced obese model, we further showed that
sesamin improved the high-fat diet induced decrease in irisin production and secretion, which results in an improvement of
body weight gain and skeletal muscle dysfunction. Our results suggested that
sesamin could activate FNDC5 expression and stimulate irisin secretion through the
SIRT1 pathway both in vitro and in vivo, which may provide a new strategy for preventing and improving irisin deficiency related diseases.