(P11-022-23) Dietary Trimethylamine N-Oxide Supplementation Improves Insulin Sensitivity and Hepatic Glucose Metabolism in High-Fat Diet Fed Mice

Objectives: To determine whether dietary TMAO supplementation affects glucose metabolism in high-fat diet (HFD) fed C57BL/6 mice.

HYPOTHESIS: Dietary TMAO supplementation will attenuate weight gain and normalize hepatic glucose metabolism in male and female mice.

Methods: 11-week-old male and female C57BL/6 mice were fed a HFD (42% fat) with or without 0.2% TMAO supplementation for 8 weeks. At weeks 5 and 6, select mice were housed in metabolic cages for 24 hours, and at week 8, select mice underwent a glucose tolerance test (GTT). Euglycemic hyperinsulinemic clamps (EGHIC) were performed on a subset of male mice. Plasma, liver, skeletal muscle, and white adipose tissue were collected following a 16-hr fast.

Results: Plasma TMAO levels were increased in TMAO-supplemented male and female mice. Weight gain was reduced in TMAO-supplemented female mice, likely due to increased whole-body oxygen consumption. Neither body weight or energy expenditure were altered between male groups. Both male and female TMAO-supplemented mice exhibited improved glucose tolerance, and data from EGHIC indicated insulin-stimulated glucose production was reduced in TMAO-supplemented male mice. No significant differences in fasting hepatic or plasma lipid levels, nor hepatic genes related to insulin signaling, glucose metabolism, or ER stress were observed.

Conclusions: Dietary TMAO supplementation may be beneficial for attenuating weight gain (females) and improving insulin sensitivity (both sexes) in mice fed a HFD. Further research is warranted to determine the metabolic effects of TMAO in an obesogenic state.

Funding Sources: NSERC, Alberta Diabetes Institute