D-Allulose Regulates Obesity via Endoplasmic Reticulum Stress-Mediated Glucagon-Like Peptide-1 Receptor Pathway

Summary

Obesity remains a major global health issue, with increasing focus on the incretin hormone GLP-1 and its receptor (GLP-1R) for therapeutic strategies. D-allulose is predicted to modulate GLP-1R via mechanisms linked to endoplasmic reticulum stress and ROS pathways, positively influencing GLP-1R stability and functionality. This study investigated the impact of D-allulose on adipocyte differentiation and obesity in high-fat diet (HFD)-administered and GLP-1R knockout mice over 12 weeks. D-allulose effectively regulated adipocyte differentiation by inhibiting the NADP+/NADPH-ROS-IRE1α-RIDD axis, resulting in controlled decay of GLP-1R, a newly identified RIDD target.

Key Findings

• D-allulose effectively regulated adipocyte differentiation by inhibiting the NADP+/NADPH-ROS-IRE1α-RIDD axis, resulting in controlled decay of GLP-1R, a newly identified RIDD target.
• In vivo studies revealed that D-allulose administration significantly regulated body weight and other obesity parameters in HFD-fed mice.
• These effects were not observed in GLP-1R KO mice, suggesting that the anti-obesity effects of D-allulose rely on the presence of GLP-1R.
• This study highlights the efficacy of D-allulose in controlling obesity through mechanisms dependent on GLP-1R, suggesting its potential as an effective treatment for obesity with normal GLP-1R function.

Industry Relevance

This research reinforces allulose's metabolic benefits — supporting its positioning as a functional ingredient for blood glucose management, weight control, and metabolic health. For food and beverage manufacturers, these findings provide scientific substantiation for product claims related to glycemic response and appetite regulation.

Read the full paper: Antioxidants & Redox Signaling | DOI: 10.1089/ars.2025.0158