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.

Effect of maternal baboon (Papio sp.) dietary mismatch in pregnancy and lactation on post‐natal offspring early life phenotype

“…It is noteworthy that in both groups cortisol increased after weaning at 9 months of age, confirming that weaning activates the hypothalamo-pituitaryadrenal axis in young baboons regardless of maternal diet. 13,38 In [13][14][15][16][17][18][19][20]. Sample sizes details for each timepoint in Table 2 F I G U R E 2 Male offspring morphometrics from birth through age 3 years in controls (CTR-blue; N = [14][15][16][17][18][19][20] and mismatch (MM-green; N = 4-17).…”

“…Mismatch mothers also had continuous access to a high‐fructose beverage during lactation. They were provided with both diets because animals ate more when both diets were available …”

Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

“…Considering that the first 1,000 days of life is increasingly recognized as a critical period for establishing an individual's lifelong metabolic health (3,4), it is perhaps not surprising that children from obese pregnancies have a greater risk than nonexposed children of developing obesity and components of metabolic syndrome in childhood (5,6). In rodent models, adult offspring exposed to maternal obesity and/or a calorically dense diet during gestation and lactation also have a heightened disease risk when challenged by further environmental or dietary stress (7)(8)(9). Remarkably, however, the maternal-fetal stimuli and the mechanism by which an obesogenic fetal environment (i.e., defined here as Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood.…”

Joint Effect of Maternal Plasma Homocysteine and Prepregnancy Obesity on Child Blood Pressure: A Prospective Birth Cohort Study

“…16,17 In animal and human studies, maternal obesity also has been associated with high blood Hcy levels. 18,19 From this perspective, studying the association between maternal Hcy and child BP in the presence and absence of maternal prepregnancy obesity could provide new insight into their joint association with child BP.…”