Associations between co-exposure to per- and polyfluoroalkyl substances and metabolic diseases: The mediating roles of inflammation and oxidative stress.

Sci Total Environ

Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi, Xinjiang, China; Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, China; Key Laboratory of Preventive Medicine, Shihezi University, Shihezi, Xinjiang, China; Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi, Xinjiang, China. Electronic address:

Published: November 2024

Background: Per- and polyfluoroalkyl substances (PFAS) pose potential risks to human health. In real-world settings, humans are exposed to various PFAS through numerous pathways.

Objectives: This study evaluated the associations between co-exposure to PFAS and obesity and its comorbidities, along with the mediating roles of inflammation and oxidative stress.

Methods: We analyzed 11,090 participants from National Health and Nutrition Examination Survey (NHANES), 2003-2018. Linear regression, logistic regression, and generalized additive models were used to assess the individual effects of PFAS exposure on obesity and its comorbidities. The environmental risk score (ERS) was calculated using the adaptive elastic-net model to assess the co-exposure effects. Linear and logistic regression models explored the associations between ERS and obesity and its comorbidities. Mediation analyses explored the roles of inflammatory (neutrophils, lymphocytes, and alkaline phosphatase) and oxidative stress (gamma-glutamyl transferase, total bilirubin, and uric acid) markers in the associations between ERS and obesity and its comorbidities.

Results: For each unit increase in ERS, the odds of obesity and type 2 diabetes mellitus (T2DM) increased 3.60-fold (95 % CI: 2.03, 6.38) and 1.91-fold (95 % CI: 1.28, 2.86), respectively. For each unit increase in ERS, BMI increased by 2.36 (95 % CI: 1.24, 3.48) kg/m, waist circumference increased by 6.47 (95 % CI: 3.56, 9.37) cm, and waist-to-height ratio increased by 0.04 (95 % CI: 0.02, 0.06). Lymphocytes, alkaline phosphatase, and total bilirubin were significantly associated with both ERS and obesity, with mediation proportions of 4.17 %, 3.62 %, and 7.37 %, respectively. Lymphocytes, alkaline phosphatase, total bilirubin, and uric acid were significantly associated with both ERS and T2DM, with the mediation proportions of 8.90 %, 8.74 %, 29.73 %, and 38.19 %, respectively.

Conclusions: Co-exposure to PFAS was associated with obesity and T2DM, and these associations may be mediated by inflammation and oxidative stress. Further mechanistic and prospective studies are required to verify these associations.

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Source
http://dx.doi.org/10.1016/j.scitotenv.2024.176187DOI Listing

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