title: Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in mice.
abstract: BACKGROUND
  Saturated fatty acids are thought to be of relevance for the development of non-alcoholic fatty liver disease and obesity. However, the underlying mechanisms are poorly understood. In previous studies we found that food-derived carbohydrates such as fructose alter the intestinal serotonergic system while inducing fatty liver disease in mice. Here, we examined the effect of fatty acid quantity (11% versus 15%) and quality (saturated, monounsaturated, or polyunsaturated fatty acids) on hepatic fat accumulation, intestinal barrier and the intestinal serotonergic system.
  
  
  METHODS
  C57BL/6 mice had free access to diets enriched with one of the three fatty acids or standard diet, for 8 weeks. In an additional experiment mice were fed diets enriched with saturated, monounsaturated fatty acids or standard diet supplemented with tryptophan (0.4 g/(kg.d), 8 weeks) or not. Hepatic fat accumulation, small intestinal barrier impairment and components of the serotonergic system were measured with RT-PCR, western blot or immunoassays. For statistical analysis t-test and one-way ANOVA with Tukey's post hoc test and Bartlett's test for equal variances was used.
  
  
  RESULTS
  Hepatic triglycerides, liver weight and liver to body weight ratio were significantly changed depending on the fat quality but not fat quantity. In contrast, fat quantity but not quality decreased the expression of the tight junction proteins occludin and claudin-1 in the small intestine. These changes seemed to result in enhanced portal vein endotoxin concentrations and fatty liver disease after feeding diet enriched with saturated and monounsaturated fatty acids but not polyunsaturated fatty acids. Neither fatty acid quantity nor quality significantly influenced the intestinal serotonergic system. Similarly, tryptophan supplementation had no impact on small intestinal barrier or fatty liver disease.
  
  
  CONCLUSIONS
  In conclusion, diets rich in saturated or monounsaturated fatty acids promote the development of fatty liver disease in mice, likely by a dysfunction of the small intestinal mucosal barrier.
authors: Yvonne
authors: Y
authors: Ritze
authors: Maureen
authors: M
authors: Böhle
authors: Synia
authors: S
authors: Haub
authors: Astrid
authors: A
authors: Hubert
authors: Paul
authors: P
authors: Enck
authors: Stephan
authors: S
authors: Zipfel
authors: Department of Nutritional Medicine, University of Hohenheim, Fruwirthstr, 12, 70599, Stuttgart, Germany. bischoff.stephan@uni-hohenheim.de.
authors: Stephan C
authors: SC
authors: Bischoff
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects; D004386:Duodenum / Q000378:metabolism*; D005227:Fatty Acids / Q000009:adverse effects; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009929:Organ Size; D010539:Permeability; D012701:Serotonin / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D012701:Serotonin