SCD1 methylation in subcutaneous adipose tissue associated with menopausal age

Abstract

Objective: This study was designed to investigate associations between menopausal age and the DNA methylation levels of stearoyl-coenzyme A desaturase 1 (SCD1, selected by the Illumina Human Methylation 450 K Bead Chip) and explore the changes in mRNA levels of SCD1 and DNA methyltransferases (DNMTs) in response to estrogen replacement therapy (ERT).

Methods: In the human experiment, we performed subcutaneous adipose tissue DNA extraction on 85 menopausal women. Methylation of SCD1 was measured by MethyLight polymerase chain reaction. In the rat experiment, we established models of menopause (ovariectomy group) and ERT (ovariectomy + 17β-estradiol group). The mRNA levels of SCD1, DNMT1, DNMT3A, and DNMT3B were determined.

Results: The results showed that DNA methylation of SCD1 was inversely correlated with menopausal age (r = 0.370, P < 0.001). In the rat study, the mRNA levels of SCD1 decreased (P < 0.001) and those of DNMT3A (P < 0.001) and DNMT3B increased (P < 0.001) after ERT.

Conclusion: Methylation levels of SCD1 were significantly associated with menopausal age. DNMT3A and DNMT3B may be involved in the methylation of SCD1.

摘要

目的：本研究的目的是讨论绝经年龄和硬脂酰辅酶A脱氢酶1（SCD1, 选用Illumin人甲基化450K珠片）DNA甲基化水平之间的关联, 探索SCD1在mRNA水平的变化和DNA甲基转移酶（DNMTs）对激素替代疗法（ERT）的反应。

方法：在人体实验中, 我们提取了85名更年期妇女的皮下脂肪组织中的DNA。用荧光法聚合酶链反应测定SCD1的甲基化。在大鼠实验中, 我们设立更年期模式（卵巢切除术组）和激素替代疗法（卵巢切除术+17β-雌二醇组）。测定SCD1、DNMT1、DNMT3A和DNMT3B的mRNA水平。

结果：结果表明, SCD1的DNA甲基化与绝经年龄呈负相关（r＝0.370, P < 0.001）。在大鼠实验中, ERT后SCD1的mRNA水平降低（P < 0.001）, DNMT3A的mRNA水平升高（P < 0.001）, DNMT3B的mRNA水平升高（P < 0.001）。

结论：SCD1的甲基化水平与绝经年龄显著相关。DNMT3A和DNMT3B可能参与了SCD1的甲基化。

Keywords:

• DNA methylation
• stearoyl-coenzyme A desaturase 1
• menopausal age
• estrogen replacement therapy
• DNA methyltransferases
• mRNA

Conflict of interest

The authors reported no conflict of interest. All authors contributed significantly.

Additional information

Funding

This work was supported by the Major Science and Technology Program; key projects of the Science and Technology Department of Zhejiang Province [Grant 20l4C03044-1].