title: L-arginine conjugates of bile acids-a possible treatment for non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a continuum of diseases that include simple steatosis and non-alcoholic steatohepatitis (NASH) ultimately leading to cirrhosis, hepatocellular carcinoma and end stage liver failure. Currently there is no approved treatment for NASH. It is known that bile acids not only have physiological roles in lipid digestion but also have strong hormonal properties. We have synthesized a novel chenodeoxycholyl-arginine ethyl ester conjugate (CDCArg) for the treatment of NAFLD.
  
  
  METHODS
  Chemical synthesis of CDCArg was performed. Experiments for prevention and treatment of NAFLD were carried out on C57BL/6 J male mice that were treated with high fat diet (HFD, 60% calories from fat). CDCArg or cholic acid bile acids were admixture into the diets. Food consumption, weight gain, liver histology, intraperitoneal glucose tolerance test, biochemical analysis and blood parameters were assessed at the end of the experiment after 5 weeks of diet (prevention study) or after 14 weeks of diet (treatment study). In the treatment study CDCArg was admixture into the diet at weeks 10-14.
  
  
  RESULTS
  In comparison to HFD treated mice, mice treated with HFD supplemented with CDCArg, showed reduced liver steatosis, reduced body weight and decreased testicular fat and liver tissue mass. Blood glucose, cholesterol, insulin and leptin levels were also lower in this group. No evidence of toxicity of CDCArg was recorded. In fact, liver injury, as evaluated using plasma hepatic enzyme levels, was low in mice treated with HFD and CDCArg when compared to mice treated with HFD and cholic acid.
  
  
  CONCLUSIONS
  CDCArg supplementation protected the liver against HFD-induced NAFLD without any toxic effects. These results indicate that basic amino acids e.g., L-arginine and bile acids conjugates may be a potential therapy for NAFLD.
authors.forename: Irina
authors.initials: I
authors.lastname: Voloshin
authors.forename: Michal
authors.initials: M
authors.lastname: Hahn-Obercyger
authors.forename: Sarit
authors.initials: S
authors.lastname: Anavi
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H, Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel. oren.tirosh@mail.huji.ac.il.
authors.forename: Oren
authors.initials: O
authors.lastname: Tirosh
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry*; D001835:Body Weight / Q000187:drug effects*; D002635:Chenodeoxycholic Acid / Q000737:chemistry*; D004435:Eating / Q000187:drug effects; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*
chemical_list: D004952:Esters; D002635:Chenodeoxycholic Acid; D001120:Arginine
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