Calorie restriction and pravastatin administration during pregnancy in obese rhesus macaques modulates maternal and infant metabolism and infant brain and behavioral development

Maternal obesity has been associated with a higher risk of pregnancy-related complications in mothers and offspring; however, effective interventions have not yet been developed. We tested two common interventions, calorie restriction and pravastatin administration, during pregnancy in a rhesus macaque model with the hypothesis that these interventions would normalize metabolic dysregulation in pregnant mothers leading to an improvement in infant metabolic and cognitive/social development. A total of 19 obese mothers were assigned to either one of the two intervention groups (n=5 for calorie restriction; n=7 for pravastatin) or an obese control group (n=7) with no intervention, and maternal gestational samples and postnatal infant samples were compared with lean control mothers (n=6). Gestational calorie restriction normalized one-carbon metabolism dysregulation in obese mothers but altered energy metabolism in their offspring. Although administration of pravastatin during pregnancy ten..., Study population
Pregnant female rhesus macaques (Macaca mulatta) from an indoor breeding colony at the California National Primate Research Center with appropriate social behavior and previous successful pregnancies were enrolled. Animal handling was approved by the UC Davis Institutional Animal Care and Use Committee (IACUC) (#19299). A qualitative real-time PCR assay (Jimenez & Tarantal, 2003) was used to identify mothers with male fetuses to include in this study. Since obesity is defined as subjects with body fat above 30% for women, according to guidelines from the American Society of Bariatric Physicians, American Medical Association, and in some publications (Okorodudu et al., 2010; Shah & Braverman, 2012), a Body Condition Score (BCS) of 3.5 (32.8 % body fat on average (Summers et al., 2012)) was used as the cutoff. Therefore, mothers with BCS of 3.5 and above were categorized as obese. Obese mothers were randomly assigned to the Obese Control (OC) group, OR group (rece...,