L-arginine conjugates of bile acids-a possible treatment for non-alcoholic fatty liver disease

Irina Voloshin, Michal Hahn-Obercyger, Sarit Anavi, Oren Tirosh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. Conclusion: 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.

Original languageAmerican English
Article number69
JournalLipids in Health and Disease
Volume13
Issue number1
DOIs
StatePublished - 22 Apr 2014

Bibliographical note

Funding Information:
The research was supported by a Baby seed grant to O.T. of Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.with collaboration of OneDay – Biotech and Pharma Ltd.

Keywords

  • Liver damage
  • Metabolic syndrome
  • Obesity
  • Over-nutrition
  • Steatosis

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