Sesamol Reverses Myofiber-Type Conversion in Obese States via Activating the SIRT1/AMPK Signal Pathway

Abstract

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.

Probiotic-fermented tomato with hepatic lipid metabolism modulation effects: analysis of physicochemical properties, bioactivities, and potential bioactive compounds

“…As previously emphasized in studies, phenolic compounds could regulate glucose and lipid metabolism through the activation of the AMPK signaling pathway, which supported the results of the present study. 15,47,48 These findings were consistent with our previous results on hepatic lipid metabolism protein expressions, suggesting that IF and HE in LFT could activate the AMPK pathway to reduce lipid synthesis to alleviate obesity and hepatic lipid accumulation. Notably, the concentrations of these five phenolic compounds (except IF) were significantly higher in LFT and SFT than in UFT after LP fermentation, which explains why LFT and SFT significantly increased hepatic AMPK phosphorylation levels while UFT did not.…”

Orientin Promotes Antioxidant Capacity, Mitochondrial Biogenesis, and Fiber Transformation in Skeletal Muscles through the AMPK Pathway

“…AMPK serves as a sensor for the energy status of the cell, regulating glucose utilization, maintaining mitochondrial homeostasis, participating in the regulation of muscle fiber composition. − Various phytochemicals, such as procyanidins and quercetin glycans, facilitate the transition of muscle fibers via the AMPK pathway. − Consequently, the transformation of muscle fibers is primarily governed by the AMPK/Sirt1/PGC-1α axis. , Moreover, elevated levels of mitochondrial ROS contribute to mitochondrial dysfunction and oxidative stress. NRF2 is necessary for muscle regeneration and efficient repair because it inhibits excessive inflammation-induced muscle atrophy and fibrosis and regulates satellite cell proliferation. , NRF2 activation is essential for inducing mitochondrial biogenesis and antioxidant responses, with recent studies highlighting its role in mitochondrial integrity. , …”