Beyond weight loss: lasting metabolic and anti-inflammatory effects of short-term D-allulose treatment in post-obesity models

Obesity remains a significant public health concern, with recent studies revealing that the detrimental health effects often persist even in individuals who have successfully shed excess weight. D-allulose, a low-calorie monosaccharide, has shown potential in promoting weight loss and reducing chronic inflammation associated with metabolic disorders. However, it is still unclear whether D-allulose has long-term benefits once intake is stopped. This study examined the prolonged effects of D-allulose on obesity and metaflammation. Our findings demonstrated that obese mice treated with D-allulose for one month maintained significantly lower lipid accumulation, fasting blood glucose level, glycosylated protein levels, and reduced adipose tissue inflammation compared to the Model group, even 75 days after cessation of D-allulose intake. Further cellular analyses revealed that D-allulose attenuated the activation and expression of TLR4/MyD88/NFB pathway in macrophages triggered by inflammatory stimuli. Additionally, D-allulose administration was associated with reduced protein lactylation levels in macrophages, suggesting that D-allulose may exert lasting benefits through epigenetic regulation mechanisms. These results underscore the sustained efficacy of D-allulose in combating fat accumulation, blood glucose, and inflammation, presenting a promising therapeutic approach for mitigating the residual adverse effects of obesity in individuals who have achieved weight loss.