Journal Article

The impact of a Western diet and binge drinking on metabolic dysfunction‐associated steatotic liver disease in male and female mice

Thibeault, Alec, Akili, Ihsan Shawki, Filosa, Colby, Chan, Aldi, Grenon, Jake, Miko, Corina, Young, Catherine, Wetzel, Melinda, Clubb, Virginia, Wan, Madison, Caporizzo, Matthew A., Sherman, Alanna, Skinner, R. Chris, Orlowski, Madeline, Saeed, Azhar

2026

Overview

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a major public health concern, largely driven by the high‐fat, high‐sugar and low‐fibre Western diet. The Western diet is often accompanied by binge drinking, or the rapid consumption of alcohol in a short time leading to a blood alcohol concentration of ≥0.08%. Emerging evidence suggests that co‐consumption of a Western diet and binge drinking might converge on shared pathological mechanisms in males, but little is known about the role of sex in this interaction. Given these complex interactions between diet, alcohol, sex and liver health, we sought to investigate how the addition of binge drinking to a Western diet impacts MASLD progression in male and female mice. Young (6‐week‐old) male and female C57BL6/J mice (n = 9–11 per sex per group) were assigned to the following groups: Control, Control/Binge, Western, or Western/Binge. Following 12 weeks of treatment, Western diet, regardless of binge drinking, resulted in increased hepatic lipid accumulation and oxidative damage in both sexes, with males showing more evidence of disease than females. In general, male mice in the Western binge group had the most pronounced evidence of liver damage among males, whereas female mice in the Western diet group tended to have more evidence of disease than all other female groups as measured by histology, serum transaminases and immunohistochemistry. The collective results suggest that addition of binge drinking to a Western diet can result in a more progressive form of liver disease in males and that sex plays a key role in response to the combination of unhealthy diet and binge drinking. What is the central question of this study? Does addition of binge drinking to a Western diet result in a more progressive liver disease than either alone, and how is this modulated by sex? What is the main finding and its importance? In male mice, combining binge drinking and a Western diet resulted in more pronounced detriments in key liver measures than either factor alone, whereas females showed greater liver damage in response to a Western diet alone than to the combined exposure.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Alcohol / Alcohol abuse / Animals / binge drinking / Binge Drinking - complications / Binge Drinking - metabolism / Binge Drinking - physiopathology / Blood levels / Diet / Diet, Western - adverse effects / Drinking behavior / Fatty Liver - etiology / Fatty Liver - metabolism / Female / Females / Immunohistochemistry / Lipid Metabolism - physiology / Liver - metabolism / Liver - pathology / liver disease / Liver diseases / Male / Males / Metabolic Diseases - metabolism / metabolic dysfunction‐associated steatohepatitis / metabolic dysfunction‐associated steatotic liver disease / Metabolism / Mice / Mice, Inbred C57BL / Nutrient deficiency / nutrition / Oxidative Stress - physiology / Public health / Sex / sex differences / Sex Factors / Western diet