Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, Washington.
Laboratory of Perinatal Kinesioepigenetics, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland.
Am J Physiol Regul Integr Comp Physiol. 2022 Nov 1;323(5):R728-R738. doi: 10.1152/ajpregu.00128.2022. Epub 2022 Oct 3.
Obesity in pregnancy is currently the leading cause of gestational complications for the mother and fetus worldwide. Maternal obesity (MO), common in western societies, impedes development of intestinal epithelium in the fetuses, which causes disorders in the nutrient absorption and intestine-related immune responses in offspring. Here, using a mouse model of maternal exercise (ME), we found that exercise during pregnancy protects the impairment of fetal intestinal morphometrical formation and epithelial development due to MO. MO decreased villus length and epithelial proliferation markers in E18.5 fetal small intestine, which was increased due to ME. The expression of the epithelial differentiation markers, , , and , in fetal small intestine was decreased due to MO, but protected by ME. Consistently, the biomarkers related to mitochondrial biogenesis and oxidative metabolism were downregulated in MO fetal small intestine but recovered by ME. Apelin injection to dams partially mirrored the beneficial effects of ME. ME and apelin injection activated AMPK, the downstream target of apelin receptor signaling, which might mediate the improvement of fetal epithelial development and oxidative metabolism. These findings suggest that ME, a highly accessible intervention, is effective in improving fetal intestinal epithelium of obese dams. Apelin-AMPK-mitochondrial biogenesis axis provides amenable therapeutic targets to facilitate fetal intestinal development of obese mothers.
孕期肥胖目前是全球范围内导致母婴妊娠并发症的首要原因。肥胖症（MO）在西方国家很常见，会阻碍胎儿肠上皮的发育，导致后代营养吸收和肠道相关免疫反应紊乱。在这里，我们利用母体运动（ME）的小鼠模型发现，孕期运动可预防 MO 导致的胎儿肠形态发生和上皮发育受损。MO 降低了 E18.5 胎鼠小肠的绒毛长度和上皮增殖标志物，而 ME 则增加了这些标志物的水平。MO 降低了胎儿小肠中上皮分化标志物、、、和的表达，但 ME 可对此进行保护。同样，与线粒体生物发生和氧化代谢相关的生物标志物在 MO 胎鼠小肠中下调，但 ME 可使其恢复。向母体注射 Apelin 部分模拟了 ME 的有益作用。ME 和 Apelin 注射激活了 AMPK，即 Apelin 受体信号的下游靶点，这可能介导了胎儿上皮发育和氧化代谢的改善。这些发现表明，ME 作为一种易于实施的干预措施，可有效改善肥胖母鼠的胎儿肠上皮。Apelin-AMPK-线粒体生物发生轴为肥胖母亲促进胎儿肠道发育提供了可行的治疗靶点。
