title: Oral citrulline supplementation protects female mice from the development of non-alcoholic fatty liver disease (NAFLD).
abstract: OBJECTIVE
  Impairments of intestinal barrier function are discussed as risk factors for the development and progression of non-alcoholic fatty liver disease (NAFLD). Studies suggest an association between arginine/citrulline homeostasis and the development of liver damages. Here, the effect of an oral L-citrulline (Cit) supplement on the development of a Western-style diet (WSD)-induced NAFLD was determined in mice.
  
  
  METHODS
  Female 6- to 8-week-old C57BL/6J mice were either pair-fed a liquid Western-style or control diet (C) ± 2.5 g/kg bodyweight Cit for 6 weeks (C + Cit or WSD + Cit). Indices of liver damage, glucose metabolism, intestinal barrier function and NO synthesis were measured.
  
  
  RESULTS
  While bodyweight gain was similar between groups, markers of glucose metabolism like fasting blood glucose and HOMA index and markers of liver damage like hepatic triglyceride levels, number of neutrophils and plasminogen activator inhibitor-1 protein levels were significantly lower in WSD + Cit-fed mice when compared to WSD-fed mice only. Protein levels of the tight junction proteins occludin and zonula occludens-1 in duodenum were significantly lower in mice fed a WSD when compared to those fed a WSD + Cit (-~70 and -~60 %, respectively, P < 0.05), whereas portal endotoxin levels, concentration of 3-nitrotyrosine protein adducts in duodenum and toll-like receptor-4 mRNA expression in livers of WSD + Cit-fed mice were markedly lower than in WSD-fed mice (-~43 %, P = 0.056; -~80 and -~48 %, respectively, P < 0.05).
  
  
  CONCLUSIONS
  Our data suggest that the protective effects of supplementing Cit on the development of NAFLD in mice are associated with a decreased translocation of endotoxin into the portal vein.
authors: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Dornburger Str. 29, 07743, Jena, Germany.
authors: Cathrin
authors: C
authors: Sellmann
authors: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Dornburger Str. 29, 07743, Jena, Germany.
authors: Cheng Jun
authors: CJ
authors: Jin
authors: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Dornburger Str. 29, 07743, Jena, Germany.
authors: Anna Janina
authors: AJ
authors: Engstler
authors: Nutrition Biology Laboratory EA4466, Faculty of Pharmacy, Paris Descartes University, Sorbonne Paris Cité, Paris, France.|Clinical Chemistry Department, Paris Centre University Hospitals, APHP, Paris, France.
authors: Jean-Pascal
authors: JP
authors: De Bandt
authors: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Dornburger Str. 29, 07743, Jena, Germany. ina.bergheim@uni-jena.de.
authors: Ina
authors: I
authors: Bergheim
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002956:Citrulline / Q000494:pharmacology*; D066273:Diet, Western; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D007328:Insulin; D062793:Occludin; C568986:Ocln protein, mouse; D017395:Plasminogen Activator Inhibitor 1; D020011:Protective Agents; D062725:Tight Junction Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D062826:Zonula Occludens-1 Protein; D002956:Citrulline; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Citrulline; Endotoxin; Intestinal barrier function; Non-alcoholic fatty liver disease; Occludin