The Synergistic Effect of Binge Drinking and Western Diet on MetALD: Insights into Sex-Specific Differences

Background: Steatotic Liver Disease (SLD) affects over 35% of the US population and is primarily driven by Western diet (high sugar/ fat intake with low dietary fiber) and heavy alcohol consumption. Notably, binge drinking is the most common form of alcohol consumption among Americans and highly prevalent in young people. Although both factors are known to independently damage the liver, limited research has explored the combined impact of binge drinking and a Western diet on the development and severity of SLD, especially in both sexes. Hypothesis: We hypothesize binge drinking and Western diet will result in more severe hepatic steatosis and liver injury than either factor alone, with these effects further modulated by biological sex. Methods: Sixty-four 8-week-old C57BL/6J mice (6-10 mice/group) were assigned to one of four groups: AIN, AIN+Binge, Western, or Western+Binge where Western diet Mice were provided diet and water ad libitum with binge drinking mice receiving a 20% w/v ethanol solution 3 days/week for 6 hours/day to simulate binge drinking. Following 12 weeks of treatment, standard measures of liver health were assessed. Results: Early histological analysis displayed sex differences between male and female mice based on diet and ethanol consumption. Serum measures of transaminases and tissue measures of hepatic triglycerides also showed sex differences, with males having higher levels of each. Hepatic lipid peroxidation did not differ significantly between mice on a Western diet alone and those on a Western diet with binge drinking, in either sex. However, males on the Western diet alone showed significantly higher (P=0.04) lipid peroxidation than females on the same diet. Further targeted analyses are being performed to determine the role of sex, diet, and binge alcohol consumption on liver health. Conclusion: Early findings suggest that sex differences in hepatic steatosis may be central to disease pathogenesis which may be key to understanding its intricate mechanism. We are currently performing additional analyses to better understand the role of Western diet, binge drinking, and sex on hepatic health. Funding provided by the UVM Food Systems Research Center via a Non-Assistance Cooperative Agreement with the USDA Agricultural Research Service. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.