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- Title
Interstrain differences in liver injury and one-carbon metabolism in alcohol-fed mice.
- Authors
Tsuchiya, Masato; Ji, Cheng; Kosyk, Oksana; Shymonyak, Svitlana; Melnyk, Stepan; Kono, Hiroshi; Tryndyak, Volodymyr; Muskhelishvili, Levan; Pogribny, Igor P; Kaplowitz, Neil; Rusyn, Ivan
- Abstract
Alcoholic liver injury is a major public health issue worldwide. Even though the major mechanisms of this disease have been established over the past decades, little is known about genetic susceptibility factors that may predispose individuals who abuse alcoholic beverages to liver damage and subsequent pathological conditions. We hypothesized that a panel of genetically diverse mouse strains may be used to examine the role of endoplasmic reticulum (ER) stress and one-carbon metabolism in the mechanism of interindividual variability in alcoholic liver injury. We administered alcohol (up to 27 mg/kg/d) in a high-fat diet using an intragastric intubation model for 28 days to male mice from 14 inbred strains (129S1/SvImJ, AKR/J, BALB/cJ, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, C57BL/10J, DBA/2J, FVB/NJ, KK/HIJ, MOLF/EiJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ). Profound interstrain differences (more than 3-fold) in alcohol-induced steatohepatitis were observed among the strains in spite of consistently high levels of urine alcohol that were monitored throughout the study. We found that ER stress genes were induced only in strains with the most liver injury. Liver glutathione and methyl donor levels were affected in all strains, albeit to a different degree. The most pronounced effects that were closely associated with the degree of liver injury were hyperhomocysteinemia and strain-dependent differences in expression patterns of one-carbon metabolism-related genes.
- Publication
Hepatology (Baltimore, Md.), 2012, Vol 56, Issue 1, p130
- ISSN
1527-3350
- Publication type
Journal Article
- DOI
10.1002/hep.25641