DOI: 10.38053/acmj.1979093 ISSN: 2718-0115

The role of chlorogenic acid in palmitic acid-induced insulin resistance: regulation of IRS-1/AKT signaling, GLUT-2 levels, and oxidative stress in HepG2 cells

İnci Kurt Celep
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Aims: This study aimed to investigate the protective effects of chlorogenic acid (CGA) against palmitic acid (PA)-induced insulin resistance (IR) in human hepatocellular carcinoma cell line (HepG2) cells by evaluating its effects on antiglycation activity, inhibitory activity against diabetes-related enzymes, oxidative stress, glucose uptake, and insulin signaling pathways. Methods: The inhibitory activities of CGA against advanced glycation end products (AGEs), α-amylase, α-glucosidase, and protein tyrosine phosphatase 1B (PTP1B) were evaluated in vitro. HepG2 cells were exposed to PA to establish an IR model. Cell viability was assessed by WST-1 assay. Protein levels of IRS-1, p-AKT, GLUT-2, RAGE, and p-NF-κB were determined by Western blotting. Intracellular reactive oxygen species (ROS) levels were measured using the DCFDA fluorescence assay, whereas glucose uptake was assessed using the 2-NBDG glucose uptake assay.Results: CGA exhibited strong inhibitory effects against AGE formation, α-amylase, α-glucosidase, and PTP1B. PA treatment significantly impaired AKT phosphorylation, confirming insulin resistance. CGA restored IRS-1, p-AKT, and GLUT-2 protein levels while reducing RAGE and p-NF-κB expression. Furthermore, CGA markedly suppressed intracellular ROS production and significantly improved glucose uptake capacity in insulin-resistant HepG2 cells. Conclusion: CGA exhibited multifaceted protective effects against PA-induced IR by suppressing oxidative stress, reducing inflammatory signaling, and restoring insulin signaling pathways. These findings suggest that CGA may represent a promising natural compound for the prevention and management of hepatic insulin resistance.

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