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However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined how repeated binge\u2010like alcohol drinking in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice altered liver function, as compared with a single binge\u2010intake session and with repeated moderate alcohol consumption. We measured a number of markers associated with early\u2010 and later\u2010stage liver disruption, including liver steatosis, measures of liver cytochrome P4502E1 (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2E1) and alcohol dehydrogenase (<jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>), alcohol metabolism, expression of cytokine<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, accumulation of 4\u2010hydroxynonenal (4\u2010<jats:styled-content style=\"fixed-case\">HNE<\/jats:styled-content>) as an indicator of oxidative stress, and alanine transaminase\/aspartate transaminase as a measure of hepatocyte injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Importantly, repeated binge\u2010like alcohol drinking increased triglyceride levels in the liver and plasma, and increased lipid droplets in the liver, indicators of steatosis. In contrast, a single binge\u2010intake session or repeated moderate alcohol consumption did not alter triglyceride levels. In addition, alcohol exposure can increase rates of alcohol metabolism through<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2E1 and<jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>, which can potentially increase oxidative stress and liver dysfunction. Intermittent, excessive alcohol intake increased liver<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2E1<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, protein, and activity, as well as<jats:styled-content style=\"fixed-case\">ADH mRNA<\/jats:styled-content>and activity. Furthermore, repeated, binge\u2010like drinking, but not a single binge or moderate drinking, increased alcohol metabolism. Finally, repeated, excessive intake transiently elevated<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>for the proinflammatory cytokine<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101B and 4\u2010<jats:styled-content style=\"fixed-case\">HNE<\/jats:styled-content>levels, but did not alter markers of later\u2010stage liver hepatocyte injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, we provide data suggesting that even relatively limited binge\u2010like alcohol drinking can lead to disruptions in liver function, which might facilitate the transition to more severe forms of liver damage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13303","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T05:26:59Z","timestamp":1484890019000},"page":"345-358","source":"Crossref","is-referenced-by-count":25,"title":["Limited Excessive Voluntary Alcohol Drinking Leads to Liver 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