Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 70, Issue 7, Pages 2253-2264Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c08036
Keywords
sesamol; obesity; skeletal muscle; myofiber-type conversion; SIRT1/AMPK signal pathway
Funding
- National Natural Science Foundation of China [82073556]
- Scientific Research Project of Hunan Provincial Health Commission [202112021453]
- Natural Science Foundation of Hunan Province [2021JJ30906]
- Changsha Municipal Natural Science Foundation [kq2007074]
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Sesamol can reverse the muscle fiber-type conversion in obesity by stimulating the muscular SIRT1/AMPK signal pathway, providing a potential therapeutic strategy for obesity and obesity-related metabolic disorders.
Obesity can evoke changes of skeletal muscle structure and function, which are characterized by the conversion of myofiber from type I to type II, leading to a vicious cycle of metabolic disorders. Reversing the muscle fiber-type conversion in obese states is a novel strategy for treating those with obesity. Sesamol, a food ingredient compound isolated from sesame seeds, exerted potential antiobesity effects. The present research aimed to explore the therapeutic effects of sesamol on obesity-related skeletal muscle-fiber-type conversion and elucidate the underlying molecular mechanisms through utilizing a high-fat-diet-induced obese C57BL/6J mice model and palmitic acid-exposed C2C12 myotubes. The results showed that sesamol attenuated obesity-related metabolic disturbances, elevated exercise endurance of obese mice, and decreased lipid accumulation and insulin resistance in skeletal muscle. After the treatment with sesamol, the muscular mitochondrial content and biogenesis were increased, accompanied by the enzyme activities and myosin heavy-chain isoform changed from type II fiber to type I fiber. Mechanistic studies revealed that the effects of sesamol on reversing skeletal muscle-fiber-type conversion in obese states were associated with the stimulation of the muscular sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signal pathway, and these effects could be inhibited by a specific inhibitor of SIRT1, EX-527. In conclusion, our research provided novel evidence that sesamol could regulate myofiber-type conversion to treat obesity and obesity-related metabolic disorders by stimulating the muscular SIRT1/AMPK signal pathway.
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