A2 Refereed review article in a scientific journal
The UPR-oxidative stress nexus in diabetes and obesity: Exploring innovative therapeutic approaches for metabolic control
Authors: Akanbi, Clinton Ayodeji; Ojo, Oluwafemi Adeleke
Publisher: Elsevier BV
Publication year: 2025
Journal name in source: Obesity Medicine
Article number: 100634
Volume: 57
ISSN: 2451-8476
DOI: https://doi.org/10.1016/j.obmed.2025.100634
Web address : https://doi.org/10.1016/j.obmed.2025.100634
Maintaining cellular protein homeostasis requires the endoplasmic reticulum (ER); however, the unfolded protein response (UPR) can be triggered by the accumulation of misfolded proteins, which can cause ER stress. The goal of the UPR is to bring the body back into balance. Nevertheless, long-term ER stress can cause β-cell dysfunction and apoptosis, which greatly exacerbates metabolic diseases such as diabetes and obesity. ER stress worsens insulin resistance and reduces glucose metabolism in pancreatic β-cells. Moreover, the ER is further damaged by oxidative stress, which is defined by an excess of reactive oxygen species (ROS), which prolongs metabolic dysfunction. This review delves into the molecular mechanisms that underlie ER stress, its consequences for diabetes and obesity, and possible treatment approaches. We discuss interventions to mitigate ER stress, including chemical chaperones, UPR modulators, and dietary strategies. Current pharmacological approaches, such as chemical chaperones and UPR modulators, have demonstrated efficacy in reducing ER stress, but they often present challenges, including inconsistent treatment responses and off-target effects. Antioxidant-rich dietary strategies, while promising for long-term management, require further validation to ensure their safety and effectiveness. Additionally, advances in CRISPR–Cas9 gene-editing technology provide new opportunities for addressing genetic defects associated with these disorders. These findings emphasize the need for integrated therapies that address both oxidative and ER stress to effectively mitigate metabolic dysfunction.
Funding information in the publication:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declare that they no known financial interests that could have appeared to influence the work reported in this paper.
Acknowledgments
Dr. Oluwafemi Ojo has been co-funded by the European Union’s Horizon Europe Framework Programme for Research and Innovation 2021-2027 under the Marie Sklodowska-Curie action grant agreement No. 101126611.
