Male-Specific Effects of β-Carotene Supplementation on Lipid Metabolism in the Liver and Gonadal Adipose Tissue of Healthy Mice

Biological sex is a fundamental determinant of physiological differences, including metabolic processes and disease susceptibility. beta-carotene (BC), a provitamin A carotenoid, is known for its health benefits, but its sex-specific effects on its metabolism remain largely unexplored. This study investigated male and female BALB/c mice receiving BC or vehicle control via oral gavage for 11 weeks. Hepatic and circulating lipid levels, serum retinol, and the expression of BC cleavage enzymes (Bco1 and Bco2) and estrogen receptors (Esr1 and Esr2) in the liver and gonadal fat were analyzed. BC supplementation increased the hepatic Bco1 and Bco2 expression in males, accompanied by higher serum retinol, while downregulating expressions of these enzymes in male gonadal fat. Additionally, BC supplementation significantly reduced gonadal fat mass and adipogenic gene expression in males, with Cebpa and Esr1/Esr2 positively correlated, suggesting a role for estrogen receptor signaling in adipogenesis. These findings demonstrate that BC exerts sex- and tissue-specific effects on lipid metabolism, with strong regulatory interactions between BC metabolism, lipid homeostasis, and sex hormone signaling in males. The results provide novel insights into the mechanisms underlying sex-dependent differences in lipid metabolism following BC supplementation, with potential implications for metabolic health and disease prevention.