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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #332440
Title: Maternal obesity programs senescence signaling and glucose metabolism in osteo-progenitors from rat and human

Author
item CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item ROSE, SHANNON - Arkansas Children'S Hospital
item FRYE, RICHARD - Arkansas Children'S Hospital
item Badger, Thomas
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2016
Publication Date: 9/23/2016
Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Rose, S., Frye, R.E., Badger, T.M., Andres, A., Shankar, K. 2016. Maternal obesity programs senescence signaling and glucose metabolism in osteo-progenitors from rat and human. Endocrinology. 157(11):4172-4183. doi:10.1210/en.2016-1408.

Interpretive Summary: Effects of maternal obesity on fetal skeletal development have not been well investigated. Here, we investigated the effects of maternal obesity on fetal bone development in both rats and humans. Female rats were fed control or an obesogenic high fat diet (HFD) for 12 wks and mated with male rats fed control diets, control or HFD was continued during pregnancy. Rat fetal bone forming cells were isolated for study. We found that fetal cells from HFD obese dams showed increases in p53/p21-mediated cell senescence signaling but decreased glucose metabolism. Umbilical cord (UC) human mesenchymal stem cells (UC MSCs) from twenty four pregnant women (12 obese and 12 lean) along with placentas were collected upon delivery. The UC MSCs of obese mothers displayed less activity to develop into mature bone forming cells. These findings indicate fetal cell senescence signaling and glucose metabolism programming by maternal obesity in both rodents and humans.

Technical Abstract: Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of embryonic bone cell fate is sparse. We investigated the effects of maternal obesity on fetal osteoblast development in both rodents and humans. Female rats were fed control or an obesogenic high fat diet (HFD) for 12wks and mated with male rats fed control diets, and respective maternal diets were continued during pregnancy. Embryonic rat osteogenic calvarial cells (EOCCs) were taken from E18.5 fetuses from control and HFD dams. EOCCs from HFD obese dams showed increases in p53/p21-mediated cell senescence signaling but decreased glucose metabolism. Decreased aerobic glycolysis in HFD-EOCCs was associated with decreased osteoblastic cell differentiation and proliferation. Umbilical cord (UC) human mesenchymal stem cells (UC MSCs) from twenty four pregnant women (12 obese and 12 lean) along with placentas were collected upon delivery. The UC MSCs of obese mothers displayed less potential toward osteoblastogenesis and more towards adipogenesis. Human MSCs and placenta from obese mothers also exhibited increased cell senescence signaling, while MSCs showed decreased glucose metabolism and insulin resistance. Finally, we showed that over-expression of p53 linked increased cell senescence signaling and decreased glucose metabolism in fetal osteo-progenitors from obese rats and humans. These findings suggest programming of fetal pre-osteoblastic cell senescence signaling and glucose metabolism by maternal obesity.