AMPK-Mediated Regulation of Intestinal Barrier Function in Inflammatory Bowel Disease

Adenosine monophosphate-activated protein kinase (AMPK) serves as a central energy sensor in intestinal epithelial cells, orchestrating the assembly and maintenance of tight junctions that seal the paracellular space. In inflammatory bowel disease (IBD), dysregulated energy metabolism, oxidative stress and pro-inflammatory signalling compromise barrier integrity, leading to increased permeability, bacterial translocation and mucosal inflammation. Activation of AMPK promotes redistribution and expression of tight junction components such as occludin, claudins and zonula occludens-1, enhances autophagy of damaged organelles, and suppresses pathways of oxidative and inflammatory damage including nuclear factor-κB. Pharmacological and nutritional activators of AMPK have been shown to restore transepithelial electrical resistance, reduce cytokine production and limit epithelial apoptosis in experimental models. Beyond its cell-autonomous effects, AMPK influences immune cell polarisation and gut microbiota composition, reinforcing mucosal defence at multiple levels. These findings point to AMPK as a promising target for novel IBD therapies aimed at re-establishing barrier function, with potential to reduce dependence on broad immunosuppression and to improve long-term mucosal healing.

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AMPK-Mediated Regulation of Intestinal Barrier Function in Inflammatory Bowel Disease publication trend

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Technical terms

AMPK: A kinase that senses cellular energy status and regulates metabolic and stress-response pathways.

Tight junction: A multiprotein complex between epithelial cells that controls paracellular permeability.

TEER: Transepithelial electrical resistance, a measure of barrier integrity across cell monolayers.

Nuclear factor-κB (NF-κB): A transcription factor governing inflammatory and immune responses.

SIRT1: A deacetylase activated by AMPK that modulates stress responses and inflammation.

References

1. Arabinogalactan Alleviates Lipopolysaccharide-Induced Intestinal Epithelial Barrier Damage through Adenosine Monophosphate-Activated Protein Kinase/Silent Information Regulator 1/Nuclear Factor Kappa-B Signaling Pathways in Caco-2 Cells. International Journal of Molecular Sciences (2023).
2. Metformin protects against intestinal barrier dysfunction via AMPKα1‐dependent inhibition of JNK signalling activation. Journal of Cellular and Molecular Medicine (2017).
3. l-Arginine alleviates heat stress-induced intestinal epithelial barrier damage by promoting expression of tight junction proteins via the AMPK pathway. Molecular Biology Reports (2019).
4. AMP-activated protein kinase: a therapeutic target in intestinal diseases. Open Biology (2017).