Emily E. Grammer1, Joshua McGee2, Taylor Brown2, Marie Clunan2, Anna Huff2, Briceida Osborne2, Laura Matarese2, Walter Pories2, Joseph Houmard2, Robert Carels2, Damon L. Swift1. 1University of Virginia, Charlottesville, VA. 2East Carolina University, Greenville, NC.

BACKGROUND: Trimethylamine N-Oxide (TMAO), a metabolite produced by gut microbiota and flavin-containing monooxygenase-3 (FMO3) of the liver, is found in foods high in carnitine, choline, and lecithin (e.g., egg yolks and full-fat dairy). The oxidation of choline that leads to betaine production may also contribute to increased TMAO levels. Epidemiological studies have linked elevated TMAO concentrations with obesity and cardiovascular disease, yet there are few data regarding the effects of combined diet and exercise interventions on TMAO. METHODS: Twenty-six sedentary overweight and obese adults (Age: 47.4 ± 10.7 yrs.; Weight: 95.1 ± 13.2 kg; BMI: 34.1 ± 3.2 kg/m2) completed a 10-week exercise and hypocaloric diet intervention to obtain clinically significant weight loss of ≥7%. Aerobic exercise volume began at 300 MET min per week and increased 50 MET min weekly until 700 MET min per week was reached. For 8 weeks, the OPTIFAST program included full meal replacement (~800 daily kcal). The last 2 weeks participants could replace 2 products with whole foods and increase intake (~1400 daily kcal). Weekly classes on behavior modification were also offered. Plasma blood samples were collected at baseline and follow-up and analyzed via nuclear magnetic resonance. RESULTS: At baseline, TMAO was correlated with body weight (r=0.40, p=0.046), waist circumference (r=0.40, p=0.044), and average RMR (r=0.50, p=0.009). After the intervention, waist circumference (-7.6 cm), BMI (-3.1 kg/m2), body weight (-8.5 kg, -9.0%), and total body fat percent (-1.7%) were reduced (all ps<0.001), while there were no changes in concentrations of TMAO (-0.3 µM, p=0.292) or betaine (0.3 µM, p=0.838). There were also decreases in 2-hr OGTT glucose (-12.8 mg/dL, p=0.032) and insulin (-43.7 mg/dL, p=0.002), HOMA-IR (-2.9, p<0.001), triglycerides (-31.7 mg/dL, p<0.001), and an increase in relative VO2peak (2.4 ml/kg/min, p<0.001) following the intervention. Moreover, changes in TMAO were correlated with changes in waist circumference (r=0.50, p=0.010). Changes in betaine were correlated with average RMR changes (r=-0.42, p=0.037). CONCLUSIONS: Weight loss from a hypocaloric diet with aerobic exercise did not decrease TMAO levels, however, improvements in TMAO were associated with waist circumference reductions in overweight and obese adults. Future studies should evaluate predictors of TMAO alterations during weight maintenance.

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