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Endoplasmic Reticulum Stress-Driven Inflammatory Mediators in Metabolic Disorders: From Molecular Mechanisms to
Bo Wen1, Xiaojin Wu1, Kaiying Zhang1
1Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
Pharmacological Research
|August 8, 2026
Summary
Nutrient overload causes inflammation and endoplasmic reticulum stress (ERS), contributing to metabolic disorders. Understanding ERS pathways is key to developing therapies for conditions like type 2 diabetes and fatty liver disease.
Area of Science:
- Metabolic signaling and inflammation
- Cellular stress responses
- Endocrinology and Metabolism
Background:
- Nutrient overload triggers metaflammation, a chronic inflammatory state linked to metabolic diseases.
- The endoplasmic reticulum (ER) is sensitive to metabolic stress, leading to ER stress (ERS) and unfolded protein response (UPR) activation.
- ERS disrupts cellular function and promotes metabolic dysfunction.
Purpose of the Study:
- To review how endoplasmic reticulum stress (ERS) sensors translate metabolic stress into inflammatory signaling.
- To explore the organ-specific impacts of ERS on metabolic health.
- To summarize emerging therapeutic strategies targeting ERS.
Main Methods:
- Literature review of endoplasmic reticulum stress (ERS) and metabolic disorders.
- Analysis of signaling pathways linking UPR sensors to inflammation.
- Compilation of organ-specific consequences of ERS.
- Summary of current and emerging therapeutic interventions.
Main Results:
- Canonical UPR sensors transduce metabolic stress into pro-inflammatory cascades via transcriptional regulators and inflammasomes.
- ERS drives the production of inflammatory mediators, including cytokines, chemokines, and bioactive lipids.
- ERS contributes to tissue injury and metabolic dysfunction in organs like the liver, pancreas, adipose tissue, endothelium, and hypothalamus, creating a self-reinforcing cycle.
Conclusions:
- Endoplasmic reticulum stress is a critical mediator linking nutrient overload to metabolic dysfunction and inflammation.
- Targeting UPR pathways and organ-specific ERS offers promising therapeutic avenues for metabolic disorders.
- Disrupting the pathogenic axis of ERS is essential for restoring metabolic homeostasis.
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