Polychlorinated biphenyls induce immunometabolic switch of antiinflammatory macrophages toward an inflammatory phenotype

Abstract

Polychlorinated biphenyls (PCBs) are a group of environmental toxicants associated with increased risk of diabetes, obesity, and metabolic syndrome. These metabolic disorders are characterized by systemic and local inflammation within adipose tissue, the primary site of PCB accumulation. These inflammatory changes arise when resident adipose tissue macrophages undergo phenotypic plasticity—switching from an antiinflammatory to an inflammatory phenotype. Thus, we sought to assess whether PCB exposure drives macrophage phenotypic switching. We investigated how human monocyte-derived macrophages polarized toward an M1, M2a, or M2c phenotype were impacted by exposure to Aroclor 1254, a PCB mixture found at high levels in school air. We showed that PCB exposure not only exacerbates the inflammatory phenotype of M1 macrophages but also shifts both M2a and M2c cells toward a more inflammatory phototype in both a dose- and time-dependent manner. Additionally, we show that PCB exposure leads to significant metabolic changes. M2 macrophages exposed to PCBs exhibit increased reliance on aerobic glycolysis and reduced capacity for fatty acid and amino acid oxidation—both indicators of an inflammatory macrophage phenotype. Collectively, these results demonstrate that PCBs promote immunometabolic macrophage plasticity toward a more M1-like phenotype, thereby suggesting that PCBs exacerbate metabolic diseases by altering the inflammatory environment in adipose tissue.