Postnatal growth restriction alters myocardial mitochondrial energetics in mice

Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B-type) mice were fed a normal-protein (NP: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce similar to 20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, JO2${J_{{{\mathrm{O}}_{\mathrm{2}}}}}$) and fluorimetry (reactive oxygen species emission, JH2O2${J_{{{\mathrm{H}}_{\mathrm{2}}}{{\mathrm{O}}_{\mathrm{2}}}}}$) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin-6, voltage-dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with alpha-level of 0.05 was set a priori. Overall, PGR (7.8 +/- 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 +/- 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice. What is the central question of this study?Postnatal growth restriction (PGR) in early life is associated with cardiovascular disease: what are the mechanisms with regard to oxidative phosphorylation (OxPhos)?What is the main finding and its importance?PGR during development reduces cardiac metabolism through impairments in OxPhos. Our results show the PGR heart has higher electron leakage in the form of free radical production and reactive oxygen species emission. These findings are associated with an increased risk for cardiovascular disease in adulthood. Simply put, a brief period of growth restriction in early life has long-lasting effects on cardiac metabolism in adulthood.