Role of alcohol metabolism in non-alcoholic steatohepatitis.
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals.


RESULTS
To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4).


CONCLUSIONS
The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) alcohol concentration was elevated in the circulation of NASH patients; 2) there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD.
Baker
Susan S
SS
Department of Pediatrics, The State University of New York, Digestive Diseases and Nutrition Center, Buffalo, New York, United States of America.
Baker
Robert D
RD
Liu
Wensheng
W
Nowak
Norma J
NJ
Zhu
Lixin
L
D000293:Adolescent; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking; D000438:Alcohols / Q000378:metabolism*; D002648:Child; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation; D008099:Liver / Q000473:pathology*; D008297:Male; D009481:Neurophysins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
C438657:AVP protein, human; D000438:Alcohols; D009481:Neurophysins; D011498:Protein Precursors; D014667:Vasopressins; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; D019392:Cytochrome P-450 CYP2E1