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Title: Effect of maternal obesity on fetal bone development in the rat

Author
item CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHANG, JIAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item WYNNE, REBECCA - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 12/14/2010
Publication Date: 4/1/2011
Citation: Chen, J., Zhang, J., Lazarenko, O.P., Wynne, R.A., Blackburn, M., Ronis, M.J., Shankar, K., Badger, T.M. 2011. Effect of maternal obesity on fetal bone development in the rat. The FASEB Journal. 25(Meeting Abstracts):605.4.

Interpretive Summary: Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resistance; and hypertension. Here, we show that fetal rat bone cell forming osteogenic calvarial cells (FOCC) from obese rat dams fed a high fat diet (HFD) have significantly less potential to develop into mature osteoblasts compared to cells from AIN-93G diet-fed controls. These FOCC express lower levels of alkaline phophatase (ALP), but higher levels of PPAR' compared to fetal cells from control dams fed low fat diets (p<0.05). Microarray analysis further revealed a 15-fold decrease in the homeodomain-containing factor A10 (HoxA10) in cells from HFD offspring. ALP expression was lower (p<0.05) in control FOCC after silencing of HoxA10 gene ex vivo. Treatment of FOCC from rats fed low fat diet with an artificial mixture of free fatty acid (palmitic, stearic, oleic, linoleic and arachidonic acid in the ratio of 5:1:2:3:1 similar to that found in rat serum from HFD rats), significantly down regulated HoxA10 protein expression. These results suggest that maternal obesity may effect fetal skeletal development through down regulation of the HoxA10 gene which may lead to an increase of the prevalence of low bone mass in their offspring later in life.

Technical Abstract: Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resistance; and hypertension. Here, we show that fetal rat osteogenic calvarial cells (FOCC) from obese rat dams fed a high fat diet (HFD) have significantly less potential to develop into mature osteoblasts compared to cells from AIN-93G diet-fed controls. These FOCC express lower levels of alkaline phophatase (ALP), but higher levels of PPAR' compared to fetal cells from control dams fed low fat diets (p<0.05). Microarray analysis further revealed a 15-fold decrease in the homeodomain-containing factor A10 (HoxA10) in cells from HFD offspring. ALP expression was lower (p<0.05) in control FOCC after silencing of HoxA10 gene ex vivo. Treatment of FOCC from rats fed low fat diet with an artificial mixture of free fatty acid (palmitic, stearic, oleic, linoleic and arachidonic acid in the ratio of 5:1:2:3:1 similar to that found in rat serum from HFD rats), significantly down regulated HoxA10 protein expression. These results suggest that maternal obesity may effect fetal skeletal development through down regulation of the HoxA10 gene which may lead to an increase of the prevalence of low bone mass in their offspring later in life.