Abstract 14283: Metabolic Adaptations of the Maternal Heart During Pregnancy and Postpartum

During pregnancy, the maternal heart undergoes reversible, physiologic growth, which supports cardiac output and maintains the physiologic demands of the growing fetus and mother; however, the molecular processes underlying pregnancy-induced cardiac growth are unclear. It is well known that changes in metabolism influence cardiac remodeling, and reductions in pyruvate dehydrogenase activity and cardiac glucose oxidation have been associated with cardiac growth during pregnancy. Therefore, the goal of this study was to examine the underlying metabolic processes that contribute to the structural and functional adaptations of the heart to pregnancy. Timed pregnancy studies in 12-week-old female FVB/NJ mice showed that heart weight to tibia length (HW:TL) was increased throughout the duration of pregnancy with HW:TL being higher in mid-pregnancy (MP, 8 d pregnant), late-pregnancy (LP, 16 d pregnant), and in 1-week post birth (PB) mice versus non-pregnant, diestrus controls (NP). This hypertrophic phenotype was associated with increased myocyte cross sectional area and with significant increases in end systolic and diastolic LV volumes . Of note, we found that blood glucose levels (115 ± 4 v 151 ± 6 mg/dL; p <0.0001) were reduced at LP versus NP. RNA-seq analyses and downstream immunoblot validation revealed changes consistent with reduced cardiac glucose catabolism at LP. Specifically, we found that Pdk4 transcript and protein expression (1.00 ± 0.22 v 1.68 ± 0.08; LP v NP; p <0.03) were significantly increased at LP and phosphorylation of PFK2 was significantly reduced at LP (1.00 ± 0.12 v 0.48 ± 0.06; p <0.01) versus NP. Because inhibition of cardiac glucose oxidation may spare glucose-derived carbon for synthesis of cellular building blocks to facilitate cardiac growth using stable isotope resolved metabolomics, we found that pregnancy increased 13 C-glucose-derived carbon allocation to glycerophospholipids and amino acids suggesting that demand for biosynthetic pathway end products during pregnancy is met in part by ancillary biosynthetic pathways of glucose metabolism. Together, these findings support the hypothesis that changes in metabolism contribute to structural and functional adaptation of the heart during and after pregnancy.