Cardiac mitochondrial metabolism during pregnancy and the postpartum period.

The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-wk-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: nonpregnant (NP), midpregnancy (MP), late pregnancy (LP), and 1-wk postbirth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and postbirth (e.g., PB) compared with NP mice. Differential cardiac gene and protein expression analyses revealed changes in several mitochondrial transcripts at LP and PB, including several mitochondrial complex subunits and members of the Slc family, important for mitochondrial substrate transport. Respirometry revealed that pyruvate- and glutamate-supported state 3 respiration was significantly higher in PB vs. LP mitochondria, with respiratory control ratio (RCR) values higher in PB mitochondria. In addition, we found that PB mitochondria respired more avidly when given 3-hydroxybutyrate (3-OHB) than mitochondria from NP, MP, and LP hearts, with no differences in RCR. These increases in respiration in PB hearts occurred independent of changes in mitochondrial yield but were associated with higher abundance of 3-hydroxybutyrate dehydrogenase 1. Collectively, these findings suggest that, after birth, maternal cardiac mitochondria have an increased capacity to use 3-OHB, pyruvate, and glutamate as energy sources; however, increases in mitochondrial efficiency in the postpartum heart appear limited to carbohydrate and amino acid metabolism.NEW & NOTEWORTHY Few studies have detailed the physiological adaptations that occur in the maternal heart. We and others have shown that pregnancy-induced cardiac growth is associated with significant changes in cardiac metabolism. Here, we examined mitochondrial respiration and substrate preference in isolated mitochondria from the maternal heart. We show that following birth, cardiac mitochondria are "primed" to respire on carbohydrate, amino acid, and ketone bodies. However, heightened respiratory efficiency is observed only with carbohydrate and amino acid sources. These results suggest that significant changes in mitochondrial respiration occur in the maternal heart in the postpartum period.

Coordinated Metabolic Responses Facilitate Cardiac Growth in Pregnancy and Exercise.

PURPOSE OF REVIEW: Pregnancy and exercise are systemic stressors that promote physiological growth of the heart in response to repetitive volume overload and maintenance of cardiac output. This type of remodeling is distinct from pathological hypertrophy and involves different metabolic mechanisms that facilitate growth; however, it remains unclear how metabolic changes in the heart facilitate growth and if these processes are similar in both pregnancy- and exercise-induced cardiac growth. RECENT FINDINGS: The ability of the heart to metabolize a myriad of substrates balances cardiac demands for energy provision and anabolism. During pregnancy, coordination of hormonal status with cardiac reductions in glucose oxidation appears important for physiological growth. During exercise, a reduction in cardiac glucose oxidation also appears important for physiological growth, which could facilitate shuttling of glucose-derived carbons into biosynthetic pathways for growth. Understanding the metabolic underpinnings of physiological cardiac growth could provide insight to optimize cardiovascular health and prevent deleterious remodeling, such as that which occurs from postpartum cardiomyopathy and heart failure. This short review highlights the metabolic mechanisms known to facilitate pregnancy-induced and exercise-induced cardiac growth, both of which require changes in cardiac glucose metabolism for the promotion of growth. In addition, we mention important similarities and differences of physiological cardiac growth in these models as well as discuss current limitations in our understanding of metabolic changes that facilitate growth.