Department of Physiology, School of Medicine, Universidad Nacional de Colombia, Bogotá 11001, Colombia.
Department of Gynecology and Obstetrics, School of Medicine, Universidad Nacional de Colombia, Bogotá 11001, Colombia.
Int J Mol Sci. 2022 Aug 23;23(17):9514. doi: 10.3390/ijms23179514.
The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.
肝表达抗菌肽 2（LEAP-2）已成为内源性 GHS-R 拮抗剂，并削弱了 ghrelin 的食欲刺激作用。本研究旨在确定人类和大鼠在怀孕期间的 Ghrelin/LEAP-2 比值。在人类中，我们在观察性前瞻性队列中进行了嵌套病例对照研究。在每个妊娠期间和产后三个月研究了健康和轻度子痫前期孕妇。此外，还研究了一组非孕妇进入卵泡期和黄体期。此外，还研究了非怀孕大鼠和大鼠妊娠不同时期的 Ghrelin/LEAP-2 比值。使用市售的 ELISA 试剂盒测定人血清和大鼠血清 ghrelin 和 LEAP-2 水平。健康孕妇的 Ghrelin/LEAP-2 比值在妊娠中期左右达到峰值（p<0.05）。此外，在每个妊娠期间，健康和子痫前期孕妇的 Ghrelin/LEAP-2 比值之间没有统计学上的显著差异（p>0.05）。妊娠大鼠的 Ghrelin/LEAP-2 比值在妊娠中期左右达到峰值，与人类妊娠模式相似。通过免疫组织化学在人足月胎盘和妊娠第 12、16 和 21 天的大鼠胎盘上观察到 LEAP-2。总之，本研究首次提供了 Ghrelin/LEAP-2 比值在人类和大鼠妊娠期间妊娠中期左右达到峰值的证据，并且可能与妊娠期间体重增加率增加有关。因此，本研究表明 LEAP-2 和 Ghrelin/LEAP-2 比值可能在妊娠期间体重增加的母体生理学适应中发挥重要作用。
