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

  • Yvonne Ritze (a1), Gyöngyi Bárdos (a1), Astrid Hubert (a1), Maureen Böhle (a1) and Stephan C. Bischoff (a1)...
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 (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.

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Corresponding author
* Corresponding author: Professor Dr S. C. Bischoff, fax +49 711 459 24343, email bischoff.stephan@uni-hohenheim.de
References
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1 Byrne, CD (2012) Dorothy Hodgkin lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. Diabet Med 29, 10981107.
2 Adams, KF, Schatzkin, A, Harris, TB, et al. (2006) Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 355, 763778.
3 Adams, LA, Lymp, JF, St Sauver, J, et al. (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113121.
4 Spruss, A & Bergheim, I (2009) Dietary fructose and intestinal barrier: potential risk factor in the pathogenesis of nonalcoholic fatty liver disease. J Nutr Biochem 20, 657662.
5 Bergheim, I, Weber, S, Vos, M, et al. (2008) Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 48, 983992.
6 de Wit, NJ, Afman, LA, Mensink, M, et al. (2012) Phenotyping the effect of diet on non-alcoholic fatty liver disease. J Hepatol 57, 13701373.
7 Haub, S, Kanuri, G, Volynets, V, et al. (2010) Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice. Am J Physiol Gastrointest Liver Physiol 298, G335G344.
8 Malhi, H & Gores, GJ (2008) Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis 28, 360369.
9 Tetri, LH, Basaranoglu, M, Brunt, EM, et al. (2008) Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol 295, G987G995.
10 Thuy, S, Ladurner, R, Volynets, V, et al. (2008) Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr 138, 14521455.
11 Haub, S, Ritze, Y, Ladel, I, et al. (2011) Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice. J Pharmacol Exp Ther 339, 790798.
12 Weber, S, Volynets, V, Kanuri, G, et al. (2009) Treatment with the 5-HT3 antagonist tropisetron modulates glucose-induced obesity in mice. Int J Obes (Lond) 33, 13391347.
13 Wade, PR, Chen, J, Jaffe, B, et al. (1996) Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 16, 23522364.
14 Gershon, MD (2004) Review Article: serotonin receptors and transporters – roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 20, Suppl. 7, 314.
15 Haub, S, Ritze, Y, Bergheim, I, et al. (2010) Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter. Neurogastroenterol Motil 22, 826834, e229.
16 Bischoff, SC, Mailer, R, Pabst, O, et al. (2009) Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice. Am J Physiol Gastrointest Liver Physiol 296, G685G695.
17 Nylander, O & Pihl, L (2006) Luminal hypotonicity increases duodenal mucosal permeability by a mechanism involving 5-hydroxytryptamine. Acta Physiol (Oxf) 186, 4558.
18 Stull, MA, Pai, V, Vomachka, AJ, et al. (2007) Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions. Proc Natl Acad Sci U S A 104, 1670816713.
19 Yamada, T, Inui, A, Hayashi, N, et al. (2003) Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum. Am J Physiol Gastrointest Liver Physiol 284, G782G788.
20 Noguchi, T, Nishino, M & Kido, R (1973) Tryptophan 5-hydroxylase in rat intestine. Biochem J 131, 375380.
21 Ozer, C, Gonul, B, Ercan, ZS, et al. (2007) The effect of tryptophan administration on ileum contractility and oxidant status in mice. Amino Acids 32, 453458.
22 Ozer, C, Gonul, B, Take, G, et al. (2004) Tryptophan administration increase contractility and change the ultrastructure of mice duodenum. Amino Acids 27, 215220.
23 Akiba, Y, Takahashi, K, Horiguchi, M, et al. (1992) l-Tryptophan alleviates fatty liver and modifies hepatic microsomal mixed function oxidase in laying hens. Comp Biochem Physiol Comp Physiol 102, 769774.
24 Rogers, SR & Pesti, GM (1992) Effects of tryptophan supplementation to a maize-based diet on lipid metabolism in laying hens. Br Poult Sci 33, 195200.
25 Lesurtel, M, Soll, C, Graf, R, et al. (2008) Role of serotonin in the hepato-gastrointestinal tract: an old molecule for new perspectives. Cell Mol Life Sci 65, 940952.
26 Kleiner, DE, Brunt, EM, Van Natta, M, et al. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 13131321.
27 Brun, P, Castagliuolo, I, Di Leo, V, et al. (2007) Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 292, G518G525.
28 Cani, PD, Bibiloni, R, Knauf, C, et al. (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 14701481.
29 Fears, R & Murrell, EA (1980) Tryptophan and the control of triglyceride and carbohydrate metabolism in the rat. Br J Nutr 43, 349356.
30 Teichberg, S, Wapnir, RA, Zdanowicz, M, et al. (1989) Morphologic and functional alterations in absorptive epithelial cells during l-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum. Lab Invest 60, 88101.
31 Sakurai, T, Miyazawa, S, Shindo, Y, et al. (1974) The effect of tryptophan administration on fatty acid synthesis in the liver of the fasted normal rat. Biochim Biophys Acta 360, 275288.
32 Nagano, J, Shimizu, M, Hara, T, et al. (2013) Effects of indoleamine 2,3-dioxygenase deficiency on high-fat diet-induced hepatic inflammation. PLoS One 8, e73404.
33 Turner, JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9, 799809.
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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