Vitamin A Corrects Tissue Deficits in Diet-Induced Obese Mice and Reduces Influenza Infection After Vaccination and Challenge

Objective: Individuals with obesity suffer from an increased susceptibility to severe respiratory viral infections and respond poorly to vaccinations, making it imperative to identify interventions. Recent evidence suggesting that obesity leads to tissue-specific vitamin A deficiency led to an investigation of whether high-dose oral vitamin A, a treatment used for remediating vitamin A deficiency in developing countries, could correct obesity-associated tissue deficits. Methods: Adult C57BL/6 diet-induced obese mice were supplemented with vitamin A for 4 weeks. A subset of mice were then vaccinated with inactivated influenza virus and challenged. Following supplementation, tissue vitamin A levels, lung immune cell composition, blood inflammatory cytokines, antibody responses, and viral clearance were evaluated. Results: Supplementation significantly improved vitamin A levels in lung and adipose tissues in diet-induced obese mice. Additionally, supplementation decreased inflammatory cytokines in the blood and altered the lung immune environment. Importantly, vaccinated, vitamin A–treated diet-induced obese mice exhibited improved antibody responses and significantly reduced viral loads post challenge compared with PBS-treated mice. Conclusions: Results demonstrate a low-cost intervention that may correct vitamin A tissue deficits and help control respiratory viral infections in individuals with obesity.