Artificial Sweetener, Sucralose, Accelerates Mitochondrial Respiration In Mouse Skeletal Muscle-derived Satellite Cells.

PURPOSE: Mitochondrial dysfunction in skeletal muscle is a common feature of diabetes and obesity. Artificial sweeteners (AS), including aspartame and sucralose, have been shown to have beneficial effects on glycemic control, but recent studies have raised concerns about their safety (WHO, 2023). Previous study has shown that aspartame can induce mitochondrial dysfunction in some cells (Yang C. et al., 2022). This suggests that AS may also have a negative effect on mitochondrial function in skeletal muscle. In this study, we investigated the effect of AS on mitochondrial function in mouse skeletal muscle satellite cells. METHODS: Skeletal muscle-derived satellite cells were isolated from the gastrocnemius of male C57BL/6 J mice (9-12 weeks old) and cultured. Saline (Control), 10 mM aspartame (AP), and 10 mM sucralose (SC) were added individually to the muscle satellite cells cultured for 4 days. Mitostress tests were performed using a flux analyzer, and PGC1α mRNA expression was assessed using real-time PCR in cells cultured for 7 days. RESULTS: The AS induced marked changes in skeletal muscle oxygen consumption. As expected, AP induced a reduction in oxygen consumption rate (OCR), which was significantly lower in basal respiration, maximal respiration, proton leak, ATP-dependent production, and reserve respiratory capacity (+60%, +52%, +62%, +59%, +49% vs. Control: p ≤ 0.05). On the other hand, surprisingly, SC induced an increase in OCR, which was reflected in significant increases in basal respiration, maximal respiration, proton leak, ATP-dependent production, and reserve respiratory capacity (+162%, +161%, +169%, +159%, +154% vs. Control: p ≤ 0.05). In addition, SC significantly increased PGC1α mRNA expression (vs. control: p ≤ 0.01). CONCLUSIONS: Aspartame may induce mitochondrial dysfunction in skeletal muscle cells, whereas sucralose may improve mitochondrial function by upregulating PGC1α gene expression in skeletal muscle cells.JSPS KAKENHI JP23K10627