Dietary sucrose, sucralose and probiotic sweetener isomaltooligosaccharide divergently affect exercise induced weight loss and its associated skeletal muscle metabolism

Abstract

Abstract Dietary sweeteners are highly favored by obese people who desire to lose weight and have been considered beneficial for weight maintenance and glucose control, but little is known whether they could affect exercise induced weight loss efficacy and its associated perturbations in skeletal muscles, a key organ playing critical roles glucose homeostasis. In the present study, we found daily drinking sucrose- and sucralose-sweetened water failed to influence the effect of exercise on weight reduction of high-fat-high-sucrose (HFHF) induced obese mice, but remarkably attenuated exercise induced improvements on skeletal muscle morphology, anti-fatigue capacity and glucose metabolism. Probiotic sweetener isomaltooligosaccharide (IMO) augmented beneficial effects of exercise on improving glucose metabolism and skeletal muscle morphology. Skeletal muscle transcriptomics analysis revealed that exercise regulated genes involved in fatty acid metabolism, insulin resistance, inflammation and mTOR signaling pathways. Drinking sucrose and sucralose increased mRNA expressions of Yap, IL-6, TNF-α, Fis1, Cytc, Myh2, Myh4, and protein expressions of IL-6, mTOR, FABP4 while lowered HIF1α, demonstrating their detrimental effects on counteracting exercise induced improvements in muscular functions and fatty acid metabolism. Consistent results were also validated in C2C12 skeletal muscle cells in vitro. Notably, we found that the exercised mice may be resistant to the excessive weight regain and its impaired glucose metabolism. For the first time, our study proved that both sucrose and sucralose could attenuate protection of exercise against muscular inflammation during the weight regain following weight loss. Collectively, our results reinforce that daily drinking of sucrose and sucralose-sweetened water counteracted exercise induced improvements on skeletal muscle metabolism and could be dietary factors favouring weight regain, while IMO to some extent synergistically augmented such benefits.