Accumulation of distinct persistent organic pollutants is associated with adipose tissue inflammation

Hydrophobic environmental chemicals bio-accumulate in adipose tissue (AT) in animals and humans, but their impact on diseases related to adipose tissue dysfunction remains unclear. Moreover, visceral rather than subcutaneous (SC) fat deposition is more closely associated with cardio-metabolic diseases such as type 2 diabetes, fatty liver and cardiovascular diseases. We therefore tested the hypotheses that environmental chemicals bio-accumulate in a fat depot specific pattern and that these patterns are related AT inflammation and obesity comorbidities. First, we developed an extraction method for detecting and quantifying a set of 9 persistent organic pollutants (POPs) in human AT. The quantified chemicals exhibit K_OW coefficients from 4 to 7. Paired abdominal omental and SC AT samples were obtained from 54 individuals (30 women, 24 men) with a wide range of body mass index (BMI, 16-70 kg/m²) during laparoscopic abdominal surgeries. Among the POPs are classical halogenated substances like Dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs), but also fragrance substances. We find that AT concentrations of these chemicals are neither significantly different between visceral and SC fat depots nor between women and men. However, AT bio-accumulation of distinct POPs significantly correlates with AT macrophage infiltration, adipocyte size and parameters of glucose metabolism. In both fat depots, the strongest correlations of POPs (Ethyl- tetradecanoate, 4,4'-Diisopropylbiphenyl, 2-Phenyltetralin, 2,2',4,4',5,5'-Hexachlorobiphenyl, Hexachlorobenzene) and AT macrophage infiltration were detected in lean individuals. In men with obesity, abundance of POPs correlated with the duration of obesity. Additional significant associations between AT POPs and parameters of glycemia, insulin sensitivity, and inflammation suggest that specific environmental chemicals may contribute to AT dysfunction, adipocyte hypertrophy, impaired glucose metabolism, systemic inflammation and variation in fat distribution, but not to obesity.