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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, Lyz1, Muc2, and Tff3, 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.<\/jats:p>","DOI":"10.1152\/ajpregu.00128.2022","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T07:23:12Z","timestamp":1664781792000},"page":"R728-R738","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Maternal exercise improves epithelial development of fetal intestine by enhancing apelin signaling and oxidative metabolism"],"prefix":"10.1152","volume":"323","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-3528","authenticated-orcid":false,"given":"Song Ah","family":"Chae","sequence":"first","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun 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