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Interactions Between Diet and Toxicant Exposure Lead to Increased Circulating Levels of the Cardiometabolic Disease Biomarker TMAO
Author(s) -
Petriello Michael C.,
Charnigo Richard,
Pavuk Marian,
Birnbaum Linda,
Morris Andrew,
Hennig Bernhard
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.966.11
Subject(s) - toxicant , trimethylamine n oxide , biomarker , disease , population , physiology , pollutant , environmental health , medicine , endocrinology , biology , biochemistry , trimethylamine , toxicity , ecology
Cardiovascular disorders are largely caused by genetic and environmental factors. Understanding how these factors intersect to determine individual disease risk is a critical challenge. Well‐ studied “lifestyle dependent” determinants of increased cardiovascular disease risk include smoking, physical inactivity, and poor nutrition, but emerging data now implicate exposures to persistent environmental pollutants as an important contributor to inter‐individual variability in cardiovascular disease risk. It is also critical to identify novel biomarkers that link nutrition, toxicant exposure, and cardiometabolic disease risk. Interestingly, emerging diet‐derived biomarkers such as trimethylamine‐N‐oxide (TMAO), carnitine, certain fatty acids, and choline have strong positive relationships with heart disease risk, whereas plasma levels of other nutrients, for example plant‐derived carotenoids, sterols and polyphenols are correlated with reduced risk. Quantitating levels of these nutrient biomarkers in individuals with well‐defined environmental exposures and well documented metabolic disease histories may shed light on why certain people are more or less prone to environmentally induced diseases. For example, recently, we published that in preclincial models, exposure to dioxin‐like pollutants can increase circulating levels of TMAO. In our preclinical studies, dioxin‐like PCBs strongly increase the enzyme responsible for TMAO production, FMO3, resulting in amplified increases in TMAO levels. We have now begun to investigate if these associations between pollutant exposure and TMAO are evident in the highly exposed Anniston, Alabama population. We have used mass spectrometry methods to quantitate TMAO in archived plasma samples, and have determined that higher body burden of dioxin‐like pollutants is significantly associated with increased circulating TMAO levels in humans. Support or Funding Information Supported in part by NIEHS/NIH grant P42ES007380, NCI/NIH intramural program, CDC, T32 postdoctoral training grant, and the Kentucky Agricultural Experiment Station. This research was conducted in part with resources provided by the Lexington Veterans Affairs Medical Center