Abstract MP60: Changes in Gut Microbiota Metabolite TMAO Are Related to Changes in Hepatic and Visceral Fat in Weight-loss Diet Interventions: the POUNDS Lost Trial

Abstract

Objective: Gut microbiota metabolite Trimethylamine-N-oxide (TMAO) has been related to obesity and various cardiometabolic disorders. TMAO is involved in lipid metabolism in the liver; however, little is known about whether changes in TMAO affect hepatic fat and abdominal fat distribution, and whether genetic variations modify such effects. Research Design and Methods: The present study included 92 overweight and obese participants from the POUNDS Lost trial having complete data on computed tomography (CT) scans and a genetic risk score (GRS) for nonalcoholic fatty liver disease (NAFLD). We analyzed the associations of changes in plasma TMAO with changes in hepatic fat and fat distribution from baseline to 6 months; we also assessed the interactions between the GRS and changes in TMAO. Results: Larger decreases in TMAO from baseline were significanly associated with a reduction in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and total adipose tissue (TAT) at 6 months, p=0.01, 0.02, and 0.003, respectively. In addition, we found that larger decreases in TMAO were associated with increases in HDL-cholesterol and decreases in triglycerides, p=0.02 and 0.03, respectively. Moreover, we observed significant interactions between 6-month changes in TMAO and the NAFLD GRS on the concurrent changes in liver fat (P interaction =0.007) and VAT (p interaction =0.018). Among individuals whose TMAO decreased, a lower NAFLD GRS tends to predict a greater improvement in hepatic fat and a reduction in VAT; while in those whose TMAO increased, no differences in hepatic fat or VAT were observed across the tertiles of NAFLD GRS. Conclusions: Our data indicate that changes in TMAO are related to changes in hepatic and visceral fat in weight loss diet interventions; and such relations are modified by genetic variation. Trial Registration: ClinicalTrials.gov NCT00072995.