Hernandez-Morante Juan José, Gomez-Santos Cecilia, Margareto Javier, Formiguera Xavier, Martínez Carlos Manuel, González Raquel, Martínez-Augustín Olga, Madrid Juan Antonio, Ordovas Jose María, Garaulet Marta
Department of Physiology, University of Murcia, Spain.
Age (Dordr). 2012 Dec;34(6):1369-80. doi: 10.1007/s11357-011-9309-2. Epub 2011 Sep 7.
Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.
绝经后女性表现出昼夜节律协调性的丧失，这一过程与脂肪组织的重新分布同时发生。然而，这些改变背后的具体遗传机制尚未得到研究。因此，本研究的目的是确定绝经的发生是否会导致控制人体皮下（SAT）和内脏（VAT）脂肪组织生物节律的基因发生改变，以及生物钟基因表达的变化是否与代谢综合征（MetS）风险增加有关，而代谢综合征常与绝经相关。为此，在绝经前（n = 7）和绝经后（n = 7）的女性上午相似时间采集VAT和SAT活检样本。提取RNA并进行微阵列分析。数据通过定量实时聚合酶链反应得到证实。还进行了蛋白质免疫印迹和免疫组织化学分析。当比较两组女性的生物钟基因表达时，SAT的数据显示，核心生物钟基因period3在绝经后女性中的表达显著更高，而酪蛋白激酶-1δ、E1A结合蛋白和cAMP反应元件在绝经前组中优先表达。在VAT中，period2（PER2）和v-myc髓细胞瘤病毒癌基因在绝经后组中的表达显著更高。蛋白质免疫印迹分析表明，绝经后女性中PER2和PER3蛋白表达也增加。此外，包括PER2在内的几个基因根据患者是否符合MetS标准而有差异表达。我们得出结论，绝经过渡会导致脂肪组织生物钟机制的基因型发生若干变化，这与患MetS风险增加有关。
