Instit. Maladies Métaboliques et Cardiovasculaires, I2MC, INSERM U1048, Instit. National de la Santé et de la Recherche Médicale, Toulouse, France; Dpt. of Pharmacy, Fac. Health Sciences, Univ. San Jorge, Zaragoza, Spain.
Instit. Maladies Métaboliques et Cardiovasculaires, I2MC, INSERM U1048, Instit. National de la Santé et de la Recherche Médicale, Toulouse, France; I2MC, CHU Rangueil, Univ. Paul Sabatier, Toulouse, France.
Chem Biol Interact. 2016 Oct 25;258:115-25. doi: 10.1016/j.cbi.2016.07.014. Epub 2016 Jul 28.
Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.
白皮杉醇是白藜芦醇的羟基化衍生物。虽然这两种膳食多酚都存在于可食用的植物和水果中，并且在几种葡萄酒中的浓度相当，但与白藜芦醇相比，白皮杉醇对肥胖的影响研究较少。尽管白藜芦醇现在被认为可以限制各种肥胖模型中的脂肪沉积，但关于其膳食补充对人类肥胖治疗或预防的益处仍存在争议。因此，对更有效的白藜芦醇类似物的研究仍在进行中。这促使我们直接比较白皮杉醇和白藜芦醇对人体脂肪组织（hAT）的各种影响。通过在肥胖患者的皮下 hAT 样本中基于 Amplex Red 的荧光测量过氧化氢的释放。通过放射性方法、计算对接和电子顺磁共振评估了白藜芦醇和白皮杉醇与人类胺氧化酶和醌还原酶的相互作用。在小鼠脂肪细胞中比较了它们对脂肪生成和脂肪分解活性的影响。白藜芦醇和白皮杉醇分别以 18.5 和 133.7 μM 的 IC50 抑制单胺氧化酶（MAO），但不抑制 hAT 中的半卡巴嗪敏感胺氧化酶（SSAO）。对于这两种白藜芦醇，对接分数对于 MAO 优于 SSAO。白皮杉醇和白藜芦醇在有和没有 hAT 的测定中同样阻碍了过氧化氢的检测，而当与纯化的醌还原酶一起孵育时，它们具有促氧化活性。它们表现出相似的剂量依赖性抑制脂肪细胞脂肪生成活性。只有当白皮杉醇以≥100 μM 的剂量孵育时，才会抑制基础和刺激的脂肪分解。因此，白皮杉醇对脂肪细胞的作用与白藜芦醇相似，除了更强的抗脂肪分解作用外，还具有剂量依赖性。在这方面，当单独摄入或给予时，白皮杉醇可能有助于限制与肥胖相关的脂肪毒性 - 或者当与白藜芦醇同时给予时，可能会阻碍白藜芦醇诱导的脂肪动员。
