Diet, Binge Drinking, or Both? What Results in the Most Advanced Form of Liver Disease in Male and Female Mice?
Akili, Ihsan Shawki
Akili, Ihsan Shawki
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Abstract
Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) affects one third of the US population. It is driven by the Western Diet (high-fat, high-sugar, low-fiber diet) and is associated with cardiometabolic diseases. Although MASLD is mostly diet-driven, those who consume a Western diet also often do binge drinking, now the most common form of alcohol consumption. Thus, we sought to investigate whether the addition of moderate binge drinking to a Western diet fed mice would result in a more severe form of MASLD and whether these effects are influenced by sex. Young (6-week old) C57BL6/J mice (n=15-18/sex/group) were randomly assigned to one of four groups: (a) Control, (b) Control/Binge, (c) Western (d) Western/Binge. Mice were provided diet and water ad libitum while binge drinking mice received a 20% w/v ethanol solution 3-4 days/week for 4-6 hours/day to simulate binge drinking. Following 12 weeks of treatment, standard measures of liver function, oxidative damage, immune response, and metabolic markers were assessed. Hepatic Triglycerides, malondialdehyde, myeloperoxidase, reduced glutathione, and superoxide dismutase showed significant differences between groups with Western/Binge males and Western females showing the most severe damage compared to controls. Steatosis percentages by histology were above 80% in the Western and Western/Binge groups. Higher hepatic CD68, CD8 by IHC was seen in Western/Binge males compared to controls indicating steatohepatitis. Liver function tests (ALT,AST) showed significant sex differences across groups. Overall, the Western diet appears to have a more detrimental effect on liver health and function than moderate binge drinking. However, their combination led to accelerated steatohepatitis, particularly in males. Further mechanistic studies using gene expression analyses are underway to elucidate the underlying pathways.
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Date
01/01/2026
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Graduate Student
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Poster
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Animal Biosciences
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College of Agriculture and Life Sciences
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Life Science