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

Dec 2, 2025Antioxidants & redox signaling

D-Allulose may reduce obesity through a stress-related gut hormone receptor pathway

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Abstract

D-allulose significantly regulated body weight and other obesity parameters in high-fat diet-fed mice over 12 weeks.

D-allulose is predicted to influence the function and stability of the GLP-1 receptor (GLP-1R) through pathways related to endoplasmic reticulum stress and reactive oxygen species.
The compound inhibited the decay of GLP-1R by targeting a specific cellular mechanism known as the IRE1-dependent decay axis.
In high-fat diet-administered mice, D-allulose positively affected adipocyte differentiation.
The antiobesity effects of D-allulose were not observed in GLP-1R knockout mice, indicating reliance on GLP-1R function for its efficacy.

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Obesity remains a major global health issue, with the increasing focus on the incretin hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) for therapeutic strategies. D-allulose is predicted to modulate GLP-1Rmechanisms linked to endoplasmic reticulum stress and reactive oxygen species (ROS) pathways, positively influencing GLP-1R stability and functionality. This study investigates the potential of D-allulose as a therapeutic and preventive agent against obesity. It focuses on the impact of D-allulose on adipocyte differentiation and obesity in high-fat diet (HFD)-administered and GLP-1R knockout (KO) mice over 12 weeks.D-allulose effectively regulated adipocyte differentiation by inhibiting the NADP/NADPH-ROS-inositol-requiring enzyme 1α (IRE1α)-regulated IRE1-dependent decay (RIDD) axis, resulting in controlled decay of GLP-1R, a newly identified RIDD target. Furthermore,studies revealed that D-allulose administration significantly regulated body weight and other obesity parameters in HFD-fed mice. However, these effects were not observed in GLP-1R KO mice, suggesting that the antiobesity 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.43, 819-832. Aims: Results: Innovation and Conclusion: via in vivo Antioxid. Redox Signal. +

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

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