ABSTRACT
BACKGROUND AND AIMS: Moderately reduced maternal nutrient availability during pregnancy has adverse effects on the fetuses' growth and metabolism during and after pregnancy. The aim of this study was to explore effects of maternal nutrition restriction (MNR) on key metabolites of the fetal energy metabolism, particularly amino acids (AA), nonesterified fatty acids (NEFA), acylcarnitines and phospholipids. These effects may reflect mechanisms relating MNR to later adverse outcomes. METHODS AND RESULTS: Plasma and liver samples of fetal baboons, whose mothers were fed ad libitum (CTR) or MNR (70% of CTR), were collected at 0.5 and 0.9 gestation (G - term 184 days). Metabolites were measured with liquid chromatography coupled to mass spectrometry. In both, CTR and MNR, fetal metabolic profiles changed markedly between 0.5G and 0.9G. Fetal liver glucose concentrations were strongly increased. Hepatic levels of NEFA, sphingomyelins, and alkyl-linked phospholipids increased while plasma NEFA and acyl-linked phospholipids levels decreased with progression of gestation. At 0.5G, MNR fetal plasma levels of short- and medium-chain acylcarnitines were elevated, but did no longer differ between groups at 0.9G. At 0.9G, plasma levels of methionine and threonine as well as hepatic threonine levels were lower in the MNR group. CONCLUSION: Small differences in the concentrations of plasma and liver metabolites between MNR and CTR fetuses reflect good adaptation to MNR. Fetal liver metabolic profiles changed markedly between the two gestation stages, reflecting enhanced liver glucose and lipid levels with advancing gestation. Decreased concentrations of AA suggest an up-regulation of gluconeogenesis in MNR.
Subject(s)
Caloric Restriction , Fetus/metabolism , Liver/metabolism , Malnutrition/metabolism , Maternal Nutritional Physiological Phenomena , Metabolome , Adaptation, Physiological , Animals , Biomarkers/blood , Carnitine/analogs & derivatives , Carnitine/blood , Chromatography, Liquid , Disease Models, Animal , Fatty Acids, Nonesterified/blood , Female , Gestational Age , Gluconeogenesis , Humans , Malnutrition/physiopathology , Mass Spectrometry , Metabolomics/methods , Papio , Phospholipids/blood , PregnancyABSTRACT
BACKGROUND: Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. METHODS: We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. RESULTS: Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P<0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). CONCLUSION: Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.
