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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #297183
Title: Maternal obesity is associated with a lipotoxic placental environment

Author
item SABEN, JESSICA - Arkansas Children'S Nutrition Research Center (ACNC)
item LINDSEY, FORREST - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC)
item THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)
item GOMEZ-ACEVEDO, HORACIO - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2014
Publication Date: 3/1/2014
Citation: Saben, J., Lindsey, F., Zhong, Y., Thakali, K., Badger, T.M., Andres, A., Gomez-Acevedo, H., Shankar, K. 2014. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 35(3):171-7.

Interpretive Summary: Obesity has long been recognized as a high-risk obstetric condition, increasing the odds of several pregnancy-related complications. Since the placenta is in direct contact with mom’s blood, it is vulnerable to maternal signals and may play an important role in fetal programming. In this study, we utilized a method to globally assess the changes in gene expression in placenta from lean and obese women. Results from these analyses identified unique changes associated with obesity. These studies showed that maternal obesity leads increased inflammation in the placenta, with greater accumulation of lipids and signaling of inflammation-related pathways (JNK1/2 and NF-'B). These results extend our understanding of the influence of maternal obesity on the placenta and its potential role in programming of offspring health.

Technical Abstract: Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19-24 kg/m(2); n = 12) and obese groups (BMI, 32-43 kg/m(2); n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by = 1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-'B (p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1a protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress.