The Science of DioxinNovember 21, 2016 | |
Research Claims to Link Exposure to PCBs, Diet, and Cardiovascular Disease
Researchers at the University of Kentucky Superfund Research Program (“UK SRP”) Center have identified what they characterized as a new mechanism linking exposure to polychlorinated biphenyls (“PCBs”) and cardiovascular disease (“CVD”).
The researchers said that they revealed that PCBs can lead to increased production of a biological marker of CVD, which is also linked to consumption of red meat and other animal products, revealing a “novel diet-toxicant interaction” associated with CVD risk.
PCBs are a class of compounds used for decades in many industrial applications, such as electrical equipment. Although commercial production of PCBs was banned in most countries including the United States in 1979, they persist in the environment because of their stable chemical structure.
PCB Exposure and TMAO Levels in the Blood
UK SRP Center researchers led by Bernhard Hennig, Ph.D., together with Michael Petriello, Ph.D., and Andrew Morris, Ph.D., showed that exposure to PCBs in mice led to increased levels of trimethylamine N-oxide (“TMAO”) in the blood. The researchers explained that TMAO is produced when the body metabolizes foods containing certain compounds such as choline and L-carnitine, which are abundant in red meat and other animal products. When dietary precursors to TMAO are consumed, they are metabolized by gut microbiota to trimethylamine (“TMA”). TMA is then metabolized further to form TMAO by flavin-containing monooxygenases (“FMO”), particularly the FMO3 isoform.
The researchers said that they discovered that exposure to PCBs in mice increased the levels of FMO3 in the liver, increasing the circulating levels of TMAO in the blood. They observed a 100-fold increase in FMO3 mRNA expression, increased induction of the FMO3 protein, and a five-fold increase in TMAO levels in PCB-exposed mice compared to unexposed mice.
The researchers said that prior studies have linked diet to levels of TMAO in the blood but that this was the first study to identify dioxin-like PCBs as a modulator of this interaction. According to the UK SRP scientists, “this research clearly shows that, in pre-clinical models, exposure to PCBs increases the circulating levels of a biomarker of CVD risk and raises the possibility that exposure to environmental pollutants like PCBs contributes to inter-individual variability in blood TMAO levels.”
They also suggested that TMAO levels may be used as a biomarker to monitor changes in FMO3 expression and activity in PCB-exposed individuals.
The researchers said that they observed that exposure to PCBs affected the formation of TMAO by inducing FMO3 in the liver.
In other research, the researchers also are investigating whether PCBs alter the gut microbial environment, which may impact production of TMA.
The UK SRP Center research team now is working with researchers at the Centers for Disease Control and Prevention to see whether the relationship between exposure to environmental pollutants and circulating TMAO levels observed in the lab is evident in people. Using blood samples from PCB-exposed individuals from an Anniston, Alabama, cohort, they are analyzing the links between circulating PCB levels in the blood to levels of TMAO and other nutritionally relevant biological markers of disease risk.