Metabolic Signatures in Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures to Blood Pressure Five Years After Bariatric Surgery Among Adolescents.

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With one quartile increase in POP mixtures, systolic blood pressure (SBP) increased by 6.4% five years after bariatric surgery compared to baseline SBP [95% confidence interval (CI): 0.4%, 12.4%]. The meet-in-the-middle approach identified overlapping metabolic features and pathways linking POP mixtures to SBP changes, highlighting the role of prostaglandin formation via arachidonic acid metabolism. POP mixtures were negatively associated with indole-3-acetate (-0.729, 95% CI: -1.234, -0.223), which was negatively associated with SBP changes at five years (-3.49%, 95% CI: -6.51%, -0.48%). Our findings suggested that lipophilic POP mixtures attenuated the beneficial effect of bariatric surgery on improved blood pressure among adolescents via alterations in lipid metabolism.