Gouranton E, Aydemir G, Reynaud E, Marcotorchino J, Malezet C, Caris-Veyrat C, Blomhoff R, Landrier J F, Rühl R
Nutriments Lipidiques et Prévention des Maladies Métaboliques, Marseille, France.
Biochim Biophys Acta. 2011 Dec;1811(12):1105-14. doi: 10.1016/j.bbalip.2011.09.002. Epub 2011 Sep 18.
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-L1 cell model, this metabolite may have a preventative effect against inflammation, by preventing the increase in the inflammatory markers, interleukin 6 and interleukin 1β 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 2Da 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.
10'-脱辅基番茄红素酸（apo-10-番茄酸）是番茄红素的一种代谢产物，已被证明具有强大的生物活性，尤其是通过维甲酸受体（RAR）发挥作用。在本研究中，研究了其对脂肪组织和脂肪细胞的影响。在微阵列实验中，将apo-10-番茄酸处理所调控的基因集与全反式维甲酸（ATRA，RAR的天然配体）在脂肪细胞中调控的基因集进行了比较。apo-10-番茄酸处理所调控的基因中约27.5%也受ATRA调控，这表明在基因表达调控方面具有共同能力，可能是通过RAR反式激活实现的。评估了apo-10-番茄酸对脂肪组织生物学的生理影响。如果它在3T3-L1细胞模型中对脂肪生成没有影响，那么这种代谢产物可能通过在各种特定模型中防止炎症标志物白细胞介素6和白细胞介素1β的增加而具有抗炎预防作用。apo-10-番茄酸反式激活RAR以及调节RAR靶基因转录的能力在脂肪组织中进行了体内研究。虽然在脂肪组织中未检测到apo-10-番茄酸，但检测到了一种分子量比其大2Da的代谢产物，这表明脂肪组织中可能存在二氢-10'-脱辅基番茄红素酸，并且这种化合物可能激活或可能导致进一步激活RAR的apo-10-番茄酸代谢产物。由于apo-10-番茄酸处理可在脂肪组织中诱导抗炎作用但不抑制脂肪生成，我们建议apo-10-番茄酸处理及其在白色脂肪组织中的潜在活性代谢产物可考虑用于与肥胖相关病理的预防策略。
