Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Miyagi, Japan.
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Cell Metab. 2021 May 4;33(5):939-956.e8. doi: 10.1016/j.cmet.2021.03.004. Epub 2021 Mar 25.
Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.
不良的母体饮食会增加后代肥胖和 2 型糖尿病的风险，使这些疾病的发病率不断上升。相比之下，我们发现母体运动可以改善后代的代谢健康，而在这里，我们证明这是通过维生素 D 受体介导的胎盘超氧化物歧化酶 3（SOD3）表达和分泌增加来实现的。SOD3 在胎儿后代肝脏中激活 AMPK/TET 信号轴，导致葡萄糖代谢基因启动子的 DNA 去甲基化，增强肝功能并改善葡萄糖耐量。在人类中，血清和胎盘中的 SOD3 在运动的孕妇中上调。母体运动诱导的胎盘源性 SOD3 与后代肝脏之间的交叉对话的发现为改善后代代谢健康提供了一个中心机制。这些发现可能为限制代谢疾病向下一代传播提供新的治疗方法。
