Receptor‐dependent lycopene uptake in vivo: studies in scavenger receptor null mice

Abstract

Cellular uptake of various carotenoids is not well understood. Recent investigations indicate that the Class B “scavenger receptor” SR‐B1 may govern cellular uptake of b‐carotene, lutein and vitamin E. To determine whether other lipoprotein (scavenger) receptors participate in carotenoid uptake in vivo, we examined mouse strains in which the genes for specific receptors (LDL Receptor [LDLR], SR‐A, CD36) were deleted by homologous recombination. METHODS: Male mice were housed in metabolic cages and fed lycopene‐enriched (0.25 g/kg chow) or standard diets for 30 days. Four genotypes (n=12 per group) were studied: wild type, LDLR−/−, SR‐A−/− and CD36−/−. Food intake and body weight were recorded every second day. After the feeding period, plasma and tissue samples collected. Sample extracts were prepared and lycopene measured by HPLC‐UV was normalized to protein content. RESULTS: Liver lycopene accumulation (ng lycopene/g tissue) was significantly reduced in SR‐A−/−, LDLR−/− and CD36−/− mice by 85%, 67% and ~30%, respectively, compared to wild type (p<0.001). Plasma lycopene concentrations were decreased by ~50% in SR‐A−/− mice (p<0.001) but were increased by 180% in LDLR−/− mice (p<0.001). CD36−/− plasma lycopene did not significantly differ from that of wild type. Prostate gland lycopene uptake profiles were similar to the plasma lycopene results. CONCLUSIONS: In addition to SR‐B, several scavenger receptors (SR‐A, CD36 and LDLR), particularly SR‐A, are important mediators of tissue‐specific lycopene uptake in the mouse. These findings are potentially important for dietary enrichment strategies and treatment of disorders, e.g., atherosclerosis and carcinogenesis, where enhancing carotenoid uptake may reduce risk. (NIH HD42174, RR18728)