Apo-10′-lycopenoic acid impacts adipose tissue biology via the retinoic acid receptors

Apo-10'-lycopenoic acid (apo-10-lycac), a metabolite of lycopene, has been shown to possess potent biological activities, notably via the retinoic acid receptors (RAR). In the current study, its impact on adipose tissue and adipocytes was studied. In microarray experiments, the set of genes regulated by apo-10-lycac treatments was compared to the set of genes regulated by all-trans retinoic acid (ATRA), the natural ligand of RAR, in adipocytes. Approximately 27.5% of the genes regulated by apo-10-lycac treatments were also regulated by ATRA, suggesting a common ability in terms of gene expression modulation, possibly via RAR transactivation. The physiological impact of apo-10-lycac on adipose tissue biology was evaluated. If it had no effect on adipogenesis in the 3T3-Li cell model, this metabolite may have a preventative effect against inflammation, by preventing the increase in the inflammatory markers, interleukin 6 and interleukin 1 beta in various dedicated models. The ability of apo-10-lycac to transactivate the RAR and to modulate the transcription of RAR target gene was brought in vivo in adipose tissue. While apo-10-lycac was not detected in adipose tissue, a metabolite with a molecular weight with 2 Da larger mass was detected, suggesting that a dihydro-apo-10'-lycopenoic acid, may be present in adipose tissue and that this compound could active or may lead to further active RAR-activating apo-10-lycac metabolites. Since apo-10-lycac treatments induce anti-inflammatory effects in adipose tissue but do not inhibit adipogenesis, we propose that apo-10-lycac treatments and its potential active metabolites in WAT may be considered for prevention strategies relevant for obesity-associated pathologies. (C) 2011 Elsevier B.V. All rights reserved.