Dietary Tryptophan Restriction Dose-Dependently Modulates Energy Balance, Gut Hormones, and Microbiota in Obesity-Prone Rats.

OBJECTIVE: To determine the effects of graded dietary restriction of tryptophan on food intake, energy expenditure, body composition, gut hormones, and select fecal bacterial populations in obesity-prone rats.

METHODS: Obesity-prone rats were randomized to isocaloric diets with varying degrees of tryptophan restriction: control (100% requirements), 70% tryptophan (70TRP), 40% tryptophan (40TRP), or 10% tryptophan (10TRP) for 21 days. The sympathetic system was challenged with a subcutaneous injection of propranolol on days 15 to 17. Measurements included food intake, energy expenditure, body composition, metabolic hormones, and fecal concentrations of select bacteria.

RESULTS: Moderate tryptophan restriction (70TRP) induced thermogenesis without altering body composition, whereas severe degrees of restriction (40TRP, 10TRP) produced profound hypophagia and decreased energy expenditure and body weight. The thermogenic effects of moderate tryptophan restriction were sympathetically mediated. Severe tryptophan restriction decreased fasting circulating concentrations of glucose, insulin, C-peptide, and leptin, but increased glucagon, pancreatic polypeptide, and glucagon-like peptide-1. Severe tryptophan restriction decreased fecal concentrations of Enterobacteriaceae, Lactobacillus, Bacteroides, and Clostridium coccoides while increasing Roseburia groups.

CONCLUSIONS: Our findings demonstrate that dietary tryptophan restriction dose-dependently modulates energy balance, with severe restriction causing hypophagia and weight loss and moderate restriction promoting sympathetically driven thermogenesis as well as concurrent changes in gut microbiota and hormones.