Wharfe Michaela D, Wyrwoll Caitlin S, Waddell Brendan J, Mark Peter J
School of Anatomy, Physiology, and Human Biology, The University of Western Australia, Perth 6009, Australia.
Endocrinology. 2016 Sep;157(9):3320-31. doi: 10.1210/en.2016-1177. Epub 2016 Jul 13.
Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57BL/6J mice before and on days 6, 10, 14, and 18 of pregnancy (term 19 d) at 4-hour intervals across a 24-hour period. Adipose expression of clock genes and downstream metabolic genes were determined by quantitative RT-PCR, and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2, and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy, with a 65% decrease in amplitude by term and a 0.61°C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic/lipogenic gene rhythms from early in gestation.
由于白色脂肪组织作为能量储存的作用以及整个孕期能量需求的动态变化，母体脂质代谢的适应性变化对于妊娠成功至关重要。因为脂质代谢受生物钟基因节律性表达的调节，所以推测母体代谢适应性变化涉及脂肪生物钟基因表达的改变以及下游代谢基因的节律性表达。研究了母体核心体温（Tc）作为驱动妊娠引起的生物钟基因表达变化的一种可能机制。在24小时内每隔4小时从C57BL/6J小鼠妊娠前以及妊娠第6、10、14和18天（足月为19天）采集性腺脂肪组织和血浆。通过定量RT-PCR测定生物钟基因和下游代谢基因的脂肪表达，并用腹腔温度记录仪测量Tc。脂肪生物钟基因表达在整个孕期呈现出强烈的节律性，但绝对水平在整个孕期有很大差异。代谢基因Lipe、Pnpla2和Lpl的节律性表达在妊娠前明显可见；然而，随着妊娠开始这种节律性消失。妊娠显著改变了Tc节律，足月时振幅降低65%，第6天至18天期间平均变化值降低0.61°C。然而，这些Tc变化在整个孕期似乎与脂肪生物钟基因表达无关。总体而言，我们的数据显示孕期脂肪生物钟有显著适应性变化，妊娠早期脂肪生物钟与脂解/脂肪生成基因节律明显解耦。
