High‐tryptophan Diet Reduces Weight Gain in Rats via Indole‐3‐propionic Acid, a Gut Microbiota Metabolite

Abstract

Tryptophan is an essential amino acid. Paradoxically, both tryptophan‐low and tryptophan‐rich diets have been found to decrease weight gain in rats, however, the mechanisms are not clear.Energy and water‐electrolyte balance were evaluated in 12‐week‐old, male, Sprague Dawley rats maintained on either control diet (TC) or tryptophan‐high (TH) or tryptophan‐low (TL) or control diet with neomycin, an antibiotic (TCA), for 10 days. Feces and blood levels of tryptophan and its bacterial metabolites were evaluated using chromatography coupled with mass spectrometry.TL rats showed reduction in body weight. TH showed body weight gain, however, it was significantly lower than in TC and TCA rats. TL rats showed significantly lower blood level of tryptophan and its bacterial derivatives including indoxyl sulfate and indole‐3‐propionic acid (I‐3‐P). TH rats had significantly higher blood tryptophan level comparing to TL rats. I‐3‐P in feces and in portal blood of TH rats was significantly higher comparing to TC, TL and TCA rats. In a separate series of experiments rats treated daily i.p. with I‐3‐P showed significantly smaller weight gain than rats treated with the vehicle.Our study suggests that tryptophan‐rich diet has a negative effect on energy balance via I‐3‐P, a gut bacteria metabolite of tryptophan. In contrast, tryptophan‐deficient diet may reduce weight due to the deficiency of the essential amino acid and decreased anabolism.Support or Funding InformationSupported by the Ministry of Science and Higher Education Republic of Poland, Diamond grant DI2016 007346This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.