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Sesamin Activates Skeletal Muscle FNDC5 Expression and Increases Irisin Secretion via the SIRT1 Signaling Pathway.

Abstract
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.
AuthorsGuangning Kou, Peiyuan Li, Yanfei Shi, Stanislav Seydou Traore, Xiaoyang Shi, Adwoa Nyantakyiwaa Amoah, Zhenwei Cui, Quanjun Lyu
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 70 Issue 25 Pg. 7704-7715 (Jun 29 2022) ISSN: 1520-5118 [Electronic] United States
PMID35708276 (Publication Type: Journal Article)
Chemical References
  • Dioxoles
  • FNDC5 protein, mouse
  • Fibronectins
  • Lignans
  • Sirt1 protein, mouse
  • Sirtuin 1
  • sesamin
Topics
  • Animals
  • Dioxoles (pharmacology)
  • Fibronectins (genetics, metabolism)
  • Lignans (pharmacology)
  • Mice
  • Muscle, Skeletal (drug effects, metabolism)
  • Obesity (drug therapy, genetics, metabolism)
  • Signal Transduction (drug effects)
  • Sirtuin 1 (genetics, metabolism)

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