Apo-12′-lycopenal, a Lycopene Metabolite, Promotes Adipocyte Differentiation via Peroxisome Proliferator-Activated Receptor γ Activation

Apo-lycopenals, lycopene metabolites produced by an initial cleavage by beta,beta-carotene-9',10'-oxygenase, exhibit diverse biologically active effects. In this study, we investigated the effect of apo-lycopenals on the activation of nuclear receptors involved in glucose and lipid metabolism. Only apo-12'-lycopenal exhibited selective and dose-dependent transactivation activity for peroxisome proliferator-activated receptor gamma (PPAR gamma), whereas neither apo-6'- nor apo-8'-lycopenals displayed this activity ((7.83 +/- 0.66)-, (1.32 +/- 0.10)-, and (1.31 +/- 0.37)-fold higher activity relative to control, respectively). Additionally, apo-12'-lycopenal promoted adipocyte differentiation of 3T3-L1 cells and subsequently increased the mRNA levels of PPAR gamma (a (2.36 +/- 0.07)-fold increase relative to control; p < 0.01) and its target genes, as well as enhanced adiponectin secretion (a (3.25 +/- 0.27)-fold increase relative to control; p < 0.01) and insulin-stimulated glucose uptake (1486 +/- 85 pmol/well; p < 0.001) in 3T3-L1 cells. Our results indicated that apo-12'-lycopenal promoted adipocyte differentiation by direct binding and activation of PPAR gamma.