Hepatic Aquaporin 8 Promotes Alcohol Consumption and Ameliorates Alcohol-Induced Liver Injury by Facilitating Acetaldehyde Excretion.

ABSTRACT: Acetaldehyde (AcH), the first metabolite of ethanol, is an aversive and bioactive compound that plays a key role in modulating alcohol consumption and liver injury. The traditional notion is that AcH is primarily metabolized in the liver by aldehyde dehydrogenase 2 (ALDH2). However, our recent study suggests that the gut-liver ALDH2 axis, rather than the liver alone, plays a key role in metabolizing and clearing AcH partially via bile secretion. Aquaporin 8 (AQP8) is a membrane channel that localizes at the canalicular membrane of hepatocytes and is known to increase bile flow. Here, we identify hepatic AQP8 as an important channel of AcH excretion, mediating its efflux from hepatocytes into bile both with and without altering bile flow. We demonstrated that acute alcohol exposure enhanced

SUBMITTER: Chen C 

PROVIDER: S-EPMC12780843 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature