Effect of tryptophan supplementation on diet-induced non-alcoholic fatty liver disease in mice

Abstract

Intestinal serotonin (5-hydroxytrypamine, 5-HT) metabolism is thought to play a role in gut functions by regulating motility, permeability and other functions of the intestine. In the present study, we investigated the effect of tryptophan (TRP), the precursor of 5-HT, supplementation on intestinal barrier functions and non-alcoholic fatty liver disease (NAFLD). An established mouse model of NAFLD induced by feeding a fructose-rich diet (N group) was used in the present study. TRP was administered orally for 8 weeks to C57BL/6J control or NAFLD mice. NAFLD-related liver parameters (hepatic TAG and Oil Red O staining), intestinal barrier parameters (tight-junction protein occludin and portal plasma lipopolysaccharides (LPS)) and 5-HT-related parameters (5-HT, 5-HT transporter (SERT) and motility) were measured. We observed reduced duodenal occludin protein concentrations (P¼0·0007), high portal plasma LPS concentrations (P¼0·005) and an elevated liver weight:body weight ratio (P¼ 0·01) in the N group compared with the parameters in the control group. TRP supplementation led to an increase in occludin concentrations (P¼ 0·0009) and consecutively reduced liver weight:body weight ratio (P¼ 0·009) as well as overall hepatic fat accumulation in the N group (P¼ 0·05). In addition, the N group exhibited reduced SERT protein expression (P¼ 0·002), which was normalised by TRP supplementation (P¼0·02). For the first time, our data indicate that oral TRP supplementation attenuates experimental NAFLD in mice. The underlying mechanisms are not clear, but probably involve stabilisation of the intestinal barrier in the upper small intestine and amelioration of the dysregulated intestinal serotonergic system.

Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP-Activated Protein KinaseαPathway in High-Fat and High-Cholesterol Diet-Induced Nonalcoholic Fatty Liver Disease

“…45 In our study, NAFLD-induced mice showed an identical trend to those used in previous studies in that a significant increase is seen in the liver weight of NAFLDinduced mice. 2,5 In addition, we suggest that consumption of soybean embryos inhibits hepatic TG accumulation, and high-dose soybean embryos were more effective than lowdose consumption of soybean embryos. We reached this conclusion based on the significantly lower liver weights of mice fed soybean embryos.…”

“…5 The results of this study are in agreement with previous findings of studies on mice fed high-fat diets. 2,44 The NAFLD is characterized by hepatic TG accumulation. It is caused by metabolic imbalance, which results from an increase in hepatic TGs and FFAs and a decrease in the release of TGs and FFAs from the liver.…”

“…The HDinduced obesity and NAFLD is associated with hyperlipidemia, which is caused by increased TGs, LDL, and TC. 2,44,53 Previous studies have demonstrated that inhibition of lipid accumulation is caused by the activation of b-oxidation and downregulation of fatty acid synthesis through the consumption of soybeans. 44,54 In addition, the studies reported that TG, TC, and HDL cholesterol levels are changed by increases in cholesterol and synthesis of bile acid.…”

“…Several studies indicate that NAFLD-related ailments affect up to 46% of the U.S. population and 20% of the world population. 1,2 In general, >60% of obesity cases and 70-90% of diabetic patients are subject to NAFLD, 3,4 whereas only 3% of the general population is subject to this disease. 5,6 As NAFLD cases increase proportionately with the growing population of obese and diabetic patients, it is a rapidly increasing health problem worldwide.…”

The gut microbiota metabolite indole alleviates liver inflammation in mice

“…Increasing tryptophan availability for the microbiota would be the most straightforward strategy to promote indole production in vivo . Interestingly, tryptophan supplementation in mice was shown to modulate the progression of NAFLD, although conflicting results were obtained and the potential link with the production of indole was not explored (53, 54). In a preliminary experiment, we found that free dietary tryptophan supplementation (0.5% w/v in drinking water) in mice failed to increase indole production, as evaluated by excretion of I3S in the urine, a commonly used proxy for intestinal production of indole (55, 56).…”