Tannic Acid as a Dietary Supplement for Protection Against Metabolic Disorders Caused by Sweetened Alcohol Intake in Rats

Abstract

Excessive sugar and alcohol intake contribute to the rising prevalence of metabolic disorders. Sweetened alcoholic beverages are increasingly popular among adolescents. While the individual effects are well studied, the combined impact remains unclear. Phytochemicals show promise in managing metabolic dysfunction, but their role in sugar- and alcohol-induced metabolic damage is not well understood. This study investigated tannic acid (TA) as a potential intervention for mitigating sweetened alcohol (SAC)-induced metabolic disorders, with a focus on the liver and kidneys of young adult rats. A voluntary gelatin-based model was used to mimic adolescent alcohol shot consumption. Sixty-four male and female adolescent Sprague Dawley rats (42 days old) were treated for 10 weeks with SAC (10% ethanol + 20% fructose in gelatine) and/or TA (50 mg/kg in gelatine), or control (plain gelatine). Measurements included feed intake, body mass gain, fasting glucose, visceral fat, insulin levels, HOMA-IR, blood parameters (Hb, HCT, MCHC), and lipid profiles (TG, HDL-C, TG-HDL-C ratio). Liver absolute mass, hepatosomatic index, TBARS, and gene expression (CYP2E1, SREBP-1, IL-10, NF-κB1, TNF-α), and histology (hepatocyte density, micro/macro steatosis, fibrosis) were assessed. Kidney evaluations included mass, index, function biomarkers (KIM-1, NGAL), TBARS, and histology (urinary space, glomerular and Bowman’s capsule areas, fibrosis). All rats grew significantly (P<0.001), but body mass remained consistent within sexes. From week 3, feed intake declined in SAC and SAC+TA groups compared to PG and TA (P<0.05). SAC increased visceral fat, especially in females, and raised HDL-C levels in males (P<0.05), while other metabolic and blood markers remained unchanged (P>0.05). In females, SAC and TA each reduced hepatocyte density by ~38%, with a smaller reduction in the SAC+TA group (P<0.05). In males, SAC+TA resulted in lower hepatocyte density compared to PG and TA (P<0.05). Steatosis was more severe in females across most groups, except SAC, where males showed higher micro-vesicular steatosis (P<0.05). Hepatic fibrosis was unchanged in females but reduced in SAC and TA males (P<0.05). Kidney mass and function markers (KIM-1, NGAL) were unaffected (P>0.05), but TBARS were elevated in female kidneys (P<0.05). Urinary space was enlarged in TA and SAC females but reduced in SAC males (P<0.05). Bowman’s capsule area increased in TA females (P<0.05), with no change in males. Glomerular tuft area was higher in TA and SAC+TA females, but lower in TA males, compared to other groups (P<0.05). Moderate voluntary alcohol consumption in gelatine did not induce overt metabolic dysfunction in rats. Where abnormalities occurred, tannic acid (50 mg/kg) offered limited protection, improving only hepatic oxidative stress in males. SAC and TA had no significant impact on body mass, blood parameters, insulin resistance, triglycerides, or renal injury markers. However, SAC increased visceral fat, hepatic steatosis, lipid peroxidation, and glomerular hyperfiltration in females, while elevating HDL-C in males, suggesting greater hepatic and renal vulnerability in females. Caution is advised for females consuming sweetened alcohol.