Effect of tryptophan supplementation on diet-induced non-alcoholic fatty liver disease in mice.
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 (P= 0·0007), high portal plasma LPS concentrations (P= 0·005) and an elevated liver weight:body weight ratio (P= 0·01) in the N group compared with the parameters in the control group. TRP supplementation led to an increase in occludin concentrations (P= 0·0009) and consecutively reduced liver weight:body weight ratio (P= 0·009) as well as overall hepatic fat accumulation in the N group (P= 0·05). In addition, the N group exhibited reduced SERT protein expression (P= 0·002), which was normalised by TRP supplementation (P= 0·02). 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.
Department of Nutritional Medicine,University of Hohenheim,Fruwirthstrasse 12,Stuttgart70599,Germany.
Yvonne
Y
Ritze
Department of Nutritional Medicine,University of Hohenheim,Fruwirthstrasse 12,Stuttgart70599,Germany.
Gyöngyi
G
Bárdos
Department of Nutritional Medicine,University of Hohenheim,Fruwirthstrasse 12,Stuttgart70599,Germany.
Astrid
A
Hubert
Department of Nutritional Medicine,University of Hohenheim,Fruwirthstrasse 12,Stuttgart70599,Germany.
Maureen
M
Böhle
Department of Nutritional Medicine,University of Hohenheim,Fruwirthstrasse 12,Stuttgart70599,Germany.
Stephan C
SC
Bischoff
D000818:Animals; D001692:Biological Transport; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D004790:Enzyme Induction; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005769:Gastrointestinal Motility; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D062793:Occludin / Q000378:metabolism; D009929:Organ Size; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014364:Tryptophan / Q000627:therapeutic use*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D008070:Lipopolysaccharides; D062793:Occludin; C568986:Ocln protein, mouse; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014280:Triglycerides; D012701:Serotonin; D014364:Tryptophan; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase