Post-prandial serum concentrations of Trimethylamine-N-oxide in overweight and obese adults with low and high systemic inflammation

Abstract

Purpose: Elevated trimethylamine-N-oxide (TMAO) levels have been implicated in the development of atherosclerosis. The impact of a high-fat meal on the post-prandial TMAO response in healthy overweight and obese adults was explored, accounting for additional variables that may affect the rate of TMAO conversion. Methods: Forty overweight and obese men and women participated in a high-fat meal challenge containing 50 g fat. Blood samples were collected at fasting and hourly in the 4 hours after meal ingestion and tested for concentrations of TMAO, liver enzymes, lipids, creatinine, insulin, and inflammatory markers. An initial mixed-effects model was constructed to analyze TMAO changes in participants who classified as having low or high levels of systemic inflammation accounting for factors that may influence TMAO concentrations. Backward refinement of the initial model was performed based off p-values. Results: Model refinement found that the log TMAO response was best explained by inclusion of estimated glomerular filtration rate (eGFR), insulin over time, a linear interaction between time and inflammation phenotype, and random effects on subject. Log TMAO after the meal was not different between inflammation phenotypes (p = 0.33). Estimated GFR was the most important determinant in the log TMAO response (p = 0.03), with lower log TMAO observed with higher eGFR values. In conclusion, serum TMAO concentrations during a high fat-meal challenge were strongly determined by eGFR, but not by fasting inflammation status.