Sex‐specific hepatic effects of sweetened alcohol consumption and tannic acid intervention in adolescent rats

Abstract

This study investigated the combined effects of alcohol and sugar, termed sweetened alcohol consumption (SAC), and tannic acid (TA) intervention on hepatic health in adolescent rats. Sixty-four male and female 42-day-old Sprague-Dawley rats were assigned to control, TA (50 mg/kg), SAC (10% ethanol +20% fructose), or SAC+TA groups and treated for 10 weeks using a voluntary gelatine-based model. Growth parameters, feed intake, visceral fat, fasting glucose, insulin, HOMA-IR, lipid profiles, and hepatic outcomes, including mass, TBARS, gene expression, and histological features, were assessed. SAC reduced feed intake without affecting body mass. Females exposed to SAC showed increased visceral fat, elevated hepatic TBARS, reduced hepatocyte density, and more pronounced steatosis, indicating oxidative and structural susceptibility. In contrast, males exhibited increased HDL-cholesterol with reduced hepatic TBARS, suggesting sex-specific differences in hepatic metabolic adaptation. TA co-treatment prevented the SAC-associated increase in hepatic TBARS but did not preserve hepatocyte density or alter steatosis in females. Glucose homeostasis, insulin resistance, triglycerides, and hepatic expression of CYP2E1, SREBP-1, IL-10, NF-κB1, and TNF-α were unaffected across groups. Overall, SAC induces sex-dependent hepatic alterations during adolescence, with females showing heightened vulnerability. TA did not produce a measurable additional benefit when combined with SAC under the conditions used.