Modeling Extended Alcohol Exposure in Mice Using a Solidified Lieber-DeCarli Diet with an Optimized Feeding Box

Abstract

Alcoholic liver disease (ALD) is a significant health issue globally, arising as a consequence of excessive alcohol consumption. Currently, there is no specific pharmacotherapy for ALD, and the most effective treatment options remain abstinence or reduced alcohol intake. The Lieber-DeCarli liquid diet (LDC) has long been used to model ALD and other alcohol-related disorders in rodents. However, challenges in managing LDC, such as difficulties with food intake measurement and maintaining nutritional balance, complicate its use. To overcome these limitations, we developed a novel protocol by converting the liquid LDC into a solid form using agar, creating the solidified LDC diet (SLD). This adaptation facilitates precise control of food intake for pair-feeding and prevents nutritional deficiencies. Mice can be fed SLD either with or without 5% (w/w) ethanol over several weeks, and the addition of an oral ethanol gavage on the final day induces fatty liver and liver injury, mirroring the characteristics of ALD. This approach offers several advantages over traditional LDC, including streamlined diet preparation, consistent intake, and improved control over pair-feeding, reducing the variability of ethanol effects across subjects. The new SLD protocol promotes a more reliable modeling of ALD, contributing to more reproducible results and aiding research into pharmacological interventions for ALD and alcohol-related disorders.