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Biliverdin Reductase A (BVRA) Mediates the Gut Microbiome in Alcoholic liver disease
Author(s) -
Hamoud Abdulrizaq
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.760.1
Subject(s) - steatosis , steatohepatitis , cirrhosis , bilirubin , medicine , alcoholic liver disease , fatty liver , gut flora , intestinal permeability , liver disease , endocrinology , biology , physiology , immunology , disease
Alcohol abuse and chronic consumption are a significant medical burden in industrialized countries. Long‐term alcohol intake is associated with changes in the intestinal microbiota that increase intestinal permeability and the release of deleterious metabolites from the gut. Alcoholic liver disease (ALD) starts with the accumulation of fats in hepatocytes that may progress to alcoholic steatohepatitis (ASH), which can further advance to fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma. Plasma bilirubin levels are increased in alcoholic cirrhotic patients, which is reflective of an injurious effect to hepatocytes as a result of liver damage. In the intestine, microflora convert bilirubin to urobilinoids, which are the predominant bile pigments. We have demonstrated that a knockout of biliverdin reductase A (BVRA) in hepatocytes (hsBVRA KO) of mice, which is the enzyme that converts biliverdin to bilirubin, causes steatosis on a high‐fat diet. Recent evidence has shown that bilirubin itself is protective against hepatic lipid accumulation and obesity. We show that BVRA is suppressed in livers of mice fed alcohol. We hypothesized that BVRA is preventive of high alcohol consumption induced steatosis, which protects the liver from damage. Indeed, the hsBVRA KO mice that consume alcohol had exacerbated hepatic steatosis and changes in the gut microbiome. Together, these observations point to an early mechanism whereby high consumption of alcohol may reduce hepatic BVRA and bilirubin excretion to the gut, leading to triglyceride synthesis causing a progression toward ASH. BVRA may be a significant regulator of the gut microbiome. Future studies will investigate BVRA and bilirubin in the regulation of ALD and how they relate to the liver‐gut microbiota signaling axis. Support or Funding Information Source of Funding: This research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K01HL125445 (T.D.H.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .