# TMAO is a biomarker of dioxin-like pollutant exposure and cardiometabolic disease

> **NIH NIH R00** · WAYNE STATE UNIVERSITY · 2020 · $249,000

## Abstract

Dioxin-like organic pollutants persist in the environment and, because of their bioaccumulation in adipose
tissue can be detected in the blood of most individuals. Exposure to these pollutants causes diabetes and its
complications of obesity and cardiovascular disease in animal models. These observations can likely be
translated to humans because several large longitudinal epidemiological studies have associated serum levels
of these pollutants, for example polychlorinated biphenyls (PCBs) with an increased risk of cardiovascular
disease and type 2 diabetes. The variability in inter-individual responses to increased body burdens of these
pollutants observed in these epidemiological studies can likely be explained by the additional contributions of
genetic and other environmental risk factors, the most powerful of which is clearly the diet. The goal of this
proposal is to provide the applicant with mentored training and early career research support to become an
independent investigator studying interactions between diet, nutrition and environmental exposures as
determinants of human disease. To accomplish this the candidate will be mentored by an interactive group of
established investigators with complementary expertise in analytical chemistry, multivariate statistics, and
preclinical models of cardiovascular and metabolic disease. This training will be accomplished through
participation in an original research project studying a mechanism that could link diet and exposure to dioxin-
like persistent organic pollutants to cardiovascular disease risk. Increased circulating levels of a diet derived
metabolite, trimethylamine N-oxide (TMAO) are associated with coronary artery disease and diabetes risk in
humans. The precursor of TMAO, trimethylamine (TMA) is generated from dietary substrates (choline
containing lipids and carnitines) by the gut microbiota. TMA is oxidized to TMAO by hepatic Flavin-containing
monooxygenases, predominantly the FMO3 isoform. We have found that exposure to dioxin-like PCBs strongly
increases FMO3 expression in the liver to amplify formation of TMAO from dietary sources in animal models
and that exposure to dioxin like pollutants positively associates with circulating TMAO levels in a highly
exposed human population. These observations lead us to propose our overarching hypothesis that induction
of FMO3 expression is a mechanism linking coplanar PCB exposure to the development of cardiovascular and
related metabolic diseases and that circulating TMAO levels are a biomarker of systemic dioxin-like pollutant
exposure in humans. We will test this hypothesis in the following aims. 1: To test the hypothesis that a diet high
in TMAO precursors can exacerbate dioxin-induced cardiometabolic disease in vivo. 2: To test the hypothesis
that FMO3 and/or gut microbiota are required for dioxin-induced cardiometabolic disease in vivo. 3 To test the
hypothesis that elevated TMAO levels in dioxin-like pollutant-exposed individuals result...

## Key facts

- **NIH application ID:** 10016306
- **Project number:** 5R00ES028734-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Michael Curtis Petriello
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016306

## Citation

> US National Institutes of Health, RePORTER application 10016306, TMAO is a biomarker of dioxin-like pollutant exposure and cardiometabolic disease (5R00ES028734-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016306. Licensed CC0.

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