Adenoviral vector co-expressing ALDH1 and ADH1 mitigates alcohol toxicity and modulates glucose and lipid metabolism

Excessive alcohol consumption remains a global health concern, with ethanol and its toxic metabolite, acetaldehyde, causing significant physiological harm. Current hangover remedies fail to enhance alcohol metabolism at a fundamental level. In this study, we engineered a recombinant adenovirus, catalase 68-acetaldehyde dehydrogenase 1-alcohol dehydrogenase 1 (C68-ALDH1-ADH1), co-expressing dehydrogenases ALDH1 and ADH1 to improve alcohol metabolic capacity. In vitro and in vivo evaluations demonstrated that C68-ALDH1-ADH1 significantly reduced hepatic alcohol and acetaldehyde levels and alleviated liver injury. Overexpression of ALDH1 and ADH1 also improved glucose and lipid metabolism. Notably, the lipid metabolism related gene fatty acyl-CoA reductase 2 ( FAR2 ) was found to be associated with ALDH1/ADH1 expression, linking it to alcohol detoxification and the fatty alcohol cycle. C68-ALDH1-ADH1 further ameliorated non-alcoholic fatty liver disease (NAFLD) through this pathway. These findings supported a potential protective effect of C68-ALDH1-ADH1 in treating alcohol-related disorders.