Skeletal muscle is the largest organ in the human body, and improving energy metabolism is crucial for maintaining and promoting health, including alleviating metabolic disorders like obesity and diabetes. Piceatannol (PIC), a polyphenol in passion fruit seeds, has various beneficial effects, including blood glucose regulation, vasodilation, and antitumor activities. Although PIC has been reported to induce SIRT1 expression—a key regulator of energy metabolism—in skeletal muscle, its actual impact on metabolic function remains largely unclear. Therefore, in this study, we comprehensively analyzed the effects of PIC on energy metabolism in skeletal muscle cells. By adding PIC to C2C12 myotubes, we examined the expression of multiple metabolism-related genes and proteins—such as SIRT1, PGC1A, PDK4, and PPARG—using real-time PCR and Western blotting techniques and measured mitochondrial activity using a flux analyzer, confirming that PIC enhances energy metabolism in skeletal muscle. Additionally, we observed an increase in intracellular NAD？ levels, activation of the NAD metabolic pathway, and enhanced lipid metabolism. Furthermore, when SIRT1 expression was suppressed using siRNA, the metabolic enhancement induced by PIC was abolished, demonstrating that SIRT1 plays a central role in PIC-induced activation of skeletal muscle energy metabolism.
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