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This study investigates the levels of plasma AhR agonistic activity and its relationship with inflammatory and metabolic markers in obesity.

June 9, 2026Diabetes/Metabolism Research and Reviews0 citationsOpen Access

Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in Obesity: A Cross‐Sectional Study

FBFatemah BahmanKuwait Petroleum Corporation (Kuwait)SKShihab KochumonKuwait Petroleum Corporation (Kuwait)AMAshraf Al MadhounDasman Diabetes Institute

Key Points

This study investigates the levels of plasma AhR agonistic activity and its relationship with inflammatory and metabolic markers in obesity.
Cross-sectional design with 80 non-diabetic participants (39 obese, 23 overweight, 18 normal weight).
Plasma AhR activity measured using a luciferase reporter assay and quantified by ELISA.
Inflammatory markers analyzed with a multiplex Luminex platform.
Plasma AhR agonist activity significantly higher in obese (92.77 fold) than normal weight (51.39 fold) and overweight (67.54 fold) groups.
Positive correlations found between AhR activity and inflammatory markers like IL-1β, IL-6, and metabolic markers such as BMI and cholesterol levels.
TNF-α, MCP-1, BMI, and HDL cholesterol identified as significant predictors of AhR activity.

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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