Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in...

The aryl hydrocarbon receptor (AhR) is linked to inflammation, but its plasma agonist activity and association with metabolic and inflammatory markers in obesity remain unclear. This cross-sectional study aimed to determine the level of plasma AhR agonistic activity and its association with systemic inflammation and metabolic dysregulation in obesity.

Plasma samples were collected from 80 non-diabetic (39-obese, 23-overweight, and 18-normal/healthy weight) individuals. AhR agonist activity was assessed using a cell-based luciferase reporter assay. Plasma AhR was quantified by ELISA. Inflammatory markers were assessed using a multiplex Luminex platform.

Our findings indicate that plasma AhR agonist activity is elevated in obese (92.77 ± 4.002 fold activation) compared with normal/healthy weight (51.39 ± 2.335) and overweight participants (67.54 ± 5.24 fold activation). Moreover, the AhR protein was also elevated in obese (94.88 ± 7.62 pg/ml) compared to normal/healthy weight (65.88 ± 6.78 pg/ml) and overweight participants (67.54 ± 5.24 pg/ml), which was positively correlated with AhR activity (r = 0.441, p < 0.0001). AhR activity was positively correlated with inflammatory markers including IL-1β, IL-6, TNF-α, TNF-β, and MCP-1, as well as metabolic markers such as BMI, total cholesterol, TG, insulin, FBG, and HbA1c. In contrast, it was negatively associated with HDL cholesterol. Notably, HOMA-IR was positively correlated with AhR activity. In the regression model, TNF-α, MCP-1, BMI, and HDL cholesterol emerged as significant predictors of AhR activity.

Our findings demonstrate that elevated plasma AhR agonist activity is associated with obesity, systemic inflammation, and metabolic dysregulation. These results highlight AhR activity as a biomarker of interest and support further studies to clarify its mechanistic role and potential clinical relevance in metabolic disorders.