Eugenol alleviates dityrosine-triggered insulin resistance and LPS-related inflammatory response by modulating gut microbiota homeostasis.

Abstract

Insulin resistance (IR) is a key pathological basis of metabolic diseases. Dityrosine (Dityr), a characteristic protein oxidation product commonly present in over-processed foods, can induce IR by disrupting metabolic homeostasis. Eugenol (EUG), a natural phenolic compound with anti-inflammatory and antioxidant activities, has been shown to improve insulin sensitivity. However, its protective effect and underlying mechanism against Dityr-induced IR remain unclear. The present study aimed to investigate the effect of EUG on Dityr-induced IR in C57BL/6 mice and explore its potential mechanisms. As a result, EUG significantly improved glucose metabolism and lipid metabolism in Dityr-exposed mice in a dose-dependent manner. This study also suggested that EUG effectively decreased the levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), Toll-like receptor 4 (TLR4), nuclear factor kappa B (NFκB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and increased the level of interleukin-10 (IL-10) in Dityr-exposed mice. EUG alleviated oxidative stress induced by Dityr and upregulated the expression of the Nrf2/ARE signaling pathway. Importantly, in vivo animal experiments suggested that EUG reshaped the gut microbiota in Dityr-exposed mice at the phylum level, thereby reducing gut microbiota-derived LPS secretion and LPS-related inflammatory response. In conclusion, the effects of EUG on IR and the activation of LPS-related inflammatory response in Dityr-exposed mice might be attributed to the reconstruction of gut microbiota structure.

Key Findings

• Eugenol significantly improved glucose and lipid metabolism in dityrosine-exposed mice in a dose-dependent manner.
• Eugenol decreased levels of LPS, LBP, TLR4, NFκB, TNF-α, and IL-6, while increasing IL-10, indicating reduced inflammation.
• Eugenol alleviated oxidative stress by upregulating the Nrf2/ARE signaling pathway and reshaped gut microbiota to reduce LPS secretion and inflammation.

Clinical Significance

Citation

Chen Jia, Zhu Jingnan, Jia Qinet al.. Eugenol alleviates dityrosine-triggered insulin resistance and LPS-related inflammatory response by modulating gut microbiota homeostasis. Food & function. 2026-Oct-16.