Genetic determinants of lycopene concentration in subcutaneous adipose tissue: insights into interindividual variability in adult males

Abstract

Background and objectives: Lycopene (LYC) is a carotenoid obtained primarily from tomatoes and tomato-based products. LYC displays potent antioxidant properties and its intake and circulating concentrations have been associated with a reduced risk of prostate and breast cancers as well as cardiovascular diseases. Following absorption, it is mainly stored in adipose tissue, which accounts for approximately two-thirds of total body stores, where it may influence processes such as oxidative stress and inflammation. However, the factors determining LYC concentration in adipose tissue remain poorly understood. This study aimed to characterize the interindividual variability of adipose tissue LYC concentration and identify single nucleotide polymorphisms (SNPs) associated with it. Methods: Forty-three healthy adult males (mean age: 32.0 ± 2.0 year; mean BMI: 23.0 ± 0.3 kg m⁻²) underwent whole-genome genotyping. Periumbilical adipose tissue samples were collected on six occasions (in the fasting state and 8 h after consumption of three different standardized meals), and plasma and adipose tissue LYC concentrations were quantified by HPLC. Forty-three candidate genes potentially involved in LYC metabolism were selected, and the association of 3786 SNPs from these genes with adipose tissue LYC concentration was assessed using partial least squares regression. Results: Adipose tissue LYC concentration showed marked interindividual variability (CV = 55%). Adipose tissue and fasting plasma LYC concentrations were significantly, but moderately, correlated (Pearson's r = 0.37; 95% CI: 0.07–0.61). An internally validated PLS regression model consisting of 17 SNPs in 11 genes—ABCA1, APOB, CD36, ELOVL5, GRAMD1C, INSIG2, IRS1, ISX, PPARG, SOD2, and TCF7L2—explained 55% of the variability in adipose tissue LYC concentration (adjusted R²). Conclusions: Adipose tissue LYC concentration displays high interindividual variability, which can be explained in part by genetic variants in genes involved in carotenoid and lipid metabolism. Clinical trial registry: ClinicalTrials.gov registration number NCT02100774.