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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #350390
Title: Maternal obesity impairs skeletal development in adult offspring

Author
item CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENKOLAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHAO, HAIJUN - Arkansas Children'S Nutrition Research Center (ACNC)
item ALUND, ALEXANDER - Arkansas Children'S Hospital
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2018
Publication Date: 7/26/2018
Citation: Chen, J., Lazarenkolazarenko, O.P., Zhao, H., Alund, A.W., Shankar, K. 2018. Maternal obesity impairs skeletal development in adult offspring. Journal of Endocrinology. https://doi.org/10.1530/JOE-18-0244.
DOI: https://doi.org/10.1530/JOE-18-0244

Interpretive Summary: Maternal obesity has substantial influences on adult offspring health including increased risk of cardiovascular diseases, obesity, and early onset of degenerative bone disorders. However, studies of diet-induced maternal obesity on regulation of adult offspring bone metabolism are sparse. Here, we investigated the effects of a high fat diet (HFD)-induced maternal obesity on both fetal and adult offspring skeletal development in mice. It was discovered that HFD-induced maternal obesity significantly decreased fetal skeletal development, and this was associated with cellular senescence (cell "aging") signaling in embryonic osteo-progenitors (bone cell precursors). These results were recapitulated in human umbilical cord mesenchymal stem cells isolated from offspring of pregnant obese and normal weight mothers following delivery. Decreased fetal skeletal development persisted into adult offspring from HFD obese rodents. These findings indicate the fetal bone cell senescence signaling is regulated by maternal obesity to repress bone formation in adult offspring in rodents. The results in umbilical stem cells derived from offspring of obese mothers suggest that these effects may also manifest in humans. The studies highlight the importance of maternal metabolic health and obesity on offspring bone development.

Technical Abstract: Intrauterine or early postnatal high-fat diet (HFD) have substantial influences on adult offspring health; however, studies of HFD-induced maternal obesity on regulation of adult offspring bone formation are sparse. Here, we investigated the effects of HFD-induced maternal obesity on both fetal and adult offspring skeletal development. We found that HFD-induced maternal obesity significantly decreased fetal skeletal development, but enhanced fetal osteoblastic cell senescence signaling and significantly increased the expression of inflammatory factors of the senescence associated secretory phenotype (SASP) in osteo-progenitors. It was found that p300/CBP activation led to H3K27 acetylation to increase expression of senescence-related genes and PPARY in embryonic mouse osteogenic calvarial cells from HFD obese dams. These results were recapitulated in human umbilical cord mesenchymal stem cells (UC MSCs) isolated from offspring of pregnant obese and lean mothers following delivery. Regardless of postnatal HFD challenge, adult offspring from HFD obese dams showed significantly suppressed bone formation. Such early involution of bone formation of adult offspring from HFD obese dams may at least in part due to histone acetylation, i.e., epigenetic regulation of genes involved in cell senescence signaling in pre-osteoblasts from prenatal development. These findings indicate fetal pre-osteoblastic cell senescence signaling is epigenetically regulated by maternal obesity to repress bone formation in adult offspring in rodents, and suggest that at least some of these effects may also manifest in humans.