Grup de Recerca Nutrigenòmica i Obesitat, Laboratori de Biologia Molecular, Nutrició i Biotecnologia (LBNB), Universitat de les Illes Balears, Palma de Mallorca, Spain.
Grup de Recerca Nutrigenòmica i Obesitat, Laboratori de Biologia Molecular, Nutrició i Biotecnologia (LBNB), Universitat de les Illes Balears, Palma de Mallorca, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain; Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain.
Arch Biochem Biophys. 2018 Jul 15;650:75-84. doi: 10.1016/j.abb.2018.05.009. Epub 2018 May 11.
We previously showed that vitamin A supplementation in early life impacts white adipose tissue (WAT) biology. We here studied the vitamin's effects on DNA methylation of genes crucial for WAT cell development, determination and metabolism. CpG promoter methylation and mRNA expression of Pparg, Zfp423, Pcna, and Rbp4 was compared in inguinal WAT of 21-day-old rats supplemented during the suckling period with vehicle (controls) or an emulsion of vitamin A as retinyl ester (RE) or β-carotene (BC). The methylation profile of promoters was affected by vitamin A supplementation with pronounced differences between the RE and BC groups. In the RE group, hypermethylation of the Rbp4 (at multiple CpGs) and the Pparg2 (at a specific CpG) promoters and hypomethylation of the Pcna promoter (at multiple CpGs) was observed, together with inverse changes in gene expression levels. In the BC group, hypomethylation of the Rbp4 and hypermethylation of the Pcna promoter at distinct CpGs was observed, with no effects on gene expression. In both supplemention groups, hypomethylation and increased expression was found for Zfp423. Thus, modest vitamin A supplementation in early postnatal life impacts methylation marks in developing WAT. Differential epigenetic effects of RE and BC in early life may affect adipose tissue programming activity.
我们之前曾表明，生命早期补充维生素 A 会影响白色脂肪组织（WAT）的生物学特性。在这里，我们研究了维生素对 WAT 细胞发育、决定和代谢关键基因的 DNA 甲基化的影响。比较了哺乳期补充维生素 A 乳剂（对照组）或视黄醇酯（RE）或β-胡萝卜素（BC）的 21 天大的大鼠腹股沟 WAT 中 Pparg、Zfp423、Pcna 和 Rbp4 基因的 CpG 启动子甲基化和 mRNA 表达。维生素 A 补充会影响启动子的甲基化谱，RE 和 BC 组之间存在明显差异。在 RE 组中，观察到 Rbp4（在多个 CpG 上）和 Pparg2（在特定 CpG 上）启动子的过度甲基化以及 Pcna 启动子（在多个 CpG 上）的低甲基化，同时基因表达水平发生相反变化。在 BC 组中，观察到 Rbp4 和 Pcna 启动子在不同 CpG 上的低甲基化和高甲基化，而对基因表达没有影响。在这两个补充组中，Zfp423 的低甲基化和表达增加。因此，生命早期适度补充维生素 A 会影响正在发育的 WAT 中的甲基化标记。RE 和 BC 在生命早期的不同表观遗传效应可能会影响脂肪组织编程活性。
