Lycopene induces retinoic acid receptor transcriptional activation in mice

Abstract

Scope Lycopene is a lipophilic carotenoid and provides the red colour to tomatoes and tomato product. Various studies indicated that lycopene and tomatoes/tomato products are able to positively influence various diseases associated with a chronic inflammation. The mechanism of action of lycopene to elicit these effects is partly unknown. A possible mechanism is that biological metabolites of lycopene may activate nuclear hormone receptors in mammalian cells. The aim of this study was to investigate the potential of orally administered lycopene and all‐trans retinoic acid (ATRA) for the induction of the retinoic acid receptor (RAR) in a transgenic retinoic acid response‐element (RARE)‐reporter mouse system. Methods and results Orally administered lycopene (100 mg/kg bw in beadlets, n = 6) and ATRA as an endogenous RAR ligand (50 mg/kg bw, n = 6) for the induction of the retinoic acid receptor in male mice using a transgenic RARE‐reporter mouse system. Conclusion Lycopene treatments induced RARE‐mediated cell signalling indicated by quantified bioimaging, increased luciferase activity and up‐regulated the retinoid target genes in selected organs of the mice. We conclude that lycopene can induce RAR‐transcriptional activation in mice and lycopene might be a precursor of still non‐identified biologically active metabolites.

Reduced adiponectin expression after high‐fat diet is associated with selective up‐regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue

“…Retinoic acid response element (RARE)-Luc female mice ( n = 6) were obtained from Cgene (Oslo, Norway) and received LF, NF, or HF diets for 4 wk or the oral retinoid treatments as described before (43, 44). …”

Non-Pro-Vitamin A and Pro-Vitamin A Carotenoids in Atopy Development

“…It is present in the human organism in the trans-form but also in the form of various geometric isomers [27,28]. Up till now, there has been no direct indication that lycopene might be a pro-vitamin A carotenoid, but various studies point out that it may be a full or partial pro-vitamin A carotenoid [29]. Lycopene metabolism has only been marginally identified, but it seems to be mediated mainly via BCO-2 pathways [30,31,32].…”

“…Activation of the nuclear receptors, retinoic acid receptor (RAR), retinoid-X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) has been reported by carotenoid metabolites. The nutritional significance for the human situation is still elusive, but we expect that carotenoids other than α-/β-carotene can be metabolized to potent bioactive nuclear receptor-activating derivatives and thereby modify various important physiological effects [29,32,34,35]. …”

El tomate, ¿alimento saludable y/o funcional?

“…Otros posibles efectos beneficiosos atribuidos al licopeno han sido la inhibición de la actividad transcripcional de estrógenos (mecanismo que reduce la carcinogénesis) 21 , una asociación inversa entre el contenido de licopeno en plasma y el Índice de Masa Corporal (IMC) 38 , la protección contra la sarcopenia 39 , efecto antiinflamatorio 40 , protección de la piel frente a daños de la radiación solar 41 , y la posible reducción del riesgo de osteoporosis 42 .…”

“…La ingesta de licopeno en la dieta se hace mediante el consumo de alimentos, siendo el tomate uno de los más consumidos, y la cuestión es si es el licopeno, o hay otros factores en el tomate que sean los causantes de estos efectos 34 , o incluso si son sus metabolitos 40 . De hecho, después de la suplementación con licopeno, se han detectado algunos de los metabolitos conocidos del licopeno en tejido pulmonar de hurones 45 y en tejido hepático de ratas 46 .…”