title: Maternal obesity disrupts the methionine cycle in baboon pregnancy.
abstract: Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized that maternal obesity would dysregulate the maternal and fetal methionine cycle. To test this hypothesis, we developed a nulliparous baboon obesity model fed a high fat, high energy diet (HF-HED) prior to and during gestation, and examined methionine cycle biomarkers (e.g., circulating concentrations of homocysteine, methionine, choline, betaine, key amino acids, folate, and vitamin B-12). Animals were group housed allowing full physical activity and social interaction. Maternal prepregnancy percent body fat was 5% in controls and 19% in HF-HED mothers, while fetal weight was 16% lower in offspring of HF-HED mothers at term. Maternal and fetal homocysteine were higher, while maternal and fetal vitamin B-12 and betaine were lower in the HF-HED group. Elevations in circulating maternal folate were evident in the HF-HED group indicating impaired folate metabolism (methyl-trap) as a consequence of maternal vitamin B-12 depletion. Finally, fetal methionine, glycine, serine, and taurine were lower in the HF-HED fetuses. These data show that maternal obesity disturbs the methionine cycle in primate pregnancy, providing a mechanism for the epigenetic changes observed among obese pregnant women and suggesting diagnostic and therapeutic opportunities in human pregnancies complicated by obesity.
authors.affiliation: Center for Pregnancy and Newborn Research, Department OB/GYN, University of Texas Health Science Center San Antonio, San Antonio, Texas Texas Center for Pregnancy and Life Course Health, Southwest National Primate Research Institute Texas Biomedical Research Institute, San Antonio, Texas mac379@cornell.edu peter.nathanielsz@uwyo.edu.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.affiliation: Division of Nutritional Sciences, Savage Hall, Ithaca, New York.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California.
authors.forename: Ralph
authors.initials: R
authors.lastname: Green
authors.affiliation: Center for Pregnancy and Newborn Research, Department OB/GYN, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Mark
authors.initials: M
authors.lastname: Nijland
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Miller
authors.affiliation: Department of Animal Science and Center for Animal Biotechnology and Genomics, and Faculty of Nutrition, Texas A&M University, College Station, Texas.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Center for Pregnancy and Newborn Research, Department OB/GYN, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McDonald
authors.affiliation: Division of Nutritional Sciences, Savage Hall, Ithaca, New York mac379@cornell.edu peter.nathanielsz@uwyo.edu.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
keywords: Baboon; folate; maternal obesity; methionine cycle; vitamin B‐12, one‐carbon metabolism