The Impact of Nutrient Intake and Metabolic Wastes during Pregnancy on Offspring Hypertension: Challenges and Future Opportunities

Abstract

Hypertension can have its origin in early life. During pregnancy, many metabolic alterations occur in the mother that have a crucial role in fetal development. In response to maternal insults, fetal programming may occur after metabolic disturbance, resulting in programmed hypertension later in life. Maternal dietary nutrients act as metabolic substrates for various metabolic processes via nutrient-sensing signals. Different nutrient-sensing pathways that detect levels of sugars, amino acids, lipids and energy are integrated during pregnancy, while disturbed nutrient-sensing signals have a role in the developmental programming of hypertension. Metabolism-modulated metabolites and nutrient-sensing signals are promising targets for new drug discovery due to their pathogenic link to hypertension programming. Hence, in this review, we pay particular attention to the maternal nutritional insults and metabolic wastes affecting fetal programming. We then discuss the role of nutrient-sensing signals linking the disturbed metabolism to hypertension programming. This review also summarizes current evidence to give directions for future studies regarding how to prevent hypertension via reprogramming strategies, such as nutritional intervention, targeting nutrient-sensing signals, and reduction of metabolic wastes. Better prevention for hypertension may be possible with the help of novel early-life interventions that target altered metabolism.

Current perspectives on perinatal mental health and neurobehavioral development: focus on regulation, coregulation and self-regulation

“…We refer to [73 ▪▪ ,123] for recent overviews. We cite recent reviews addressing these complex, multifacted processes involving: mother-fetus-placenta unit [78]; HPA axis and cortisol [120,124 ▪ ,125]; autonomic nervous system [125]; iron deficiency [126]; maternal inflammation and offspring microglial activity [127]; mitochondria [128]; microbiome [10,129–131]; maternal metabolic risk factors including diabetes, obesity, undernutrition, specific macro- and micronutrient intake (e.g., long-chain polyunsaturated fatty acids (PUFAs) [132–135]; epigenetic changes, epigenome wide associations studies, relevant for e.g., the HPA axis or oxytocin system [136] including DNA methylation, histone modification, microRNA and other-non coding RNA [73 ▪▪ ,135,137–139] or multiomics data (transcriptomics, proteomics, metabolomics, and microbiomics [140]); telomere length [57]; paternal mediated effects [141,142]; oxidative stress [143], breast milk composition [78]; oxytocin system [73 ▪▪ ]; serotonin functions (e.g., SCL6A4) [73 ▪▪ ]; brain-derived neurotrophic factor (BDNF) [73 ▪▪ ]; structural and functional brain alterations beyond regions previously identified as relevant (i.e., prefrontal cortex, hippocampus, amygdala (limbic system)) additionally including basal ganglia, anterior cingulate cortex, thalamus, middle and superior frontal gyri, occipital gyrus and precentral gyrus [9,31,108].…”

Maternal High-Fat Diet Controls Offspring Kidney Health and Disease

“…In pregnancy, the maternal diet can regulate fetal metabolism and development via nutrient-sensing signals [ 119 ]. Accordingly, an imbalanced diet during gestation could disrupt nutrient-sensing signals, having a decisive impact on adult diseases of developmental origins [ 120 , 121 ].…”

“…AMPK can phosphorylate PGC-1α and regulate its downstream PPARγ signaling. Prior work indicated that specific sets of PPAR target genes participate in renal programming [ 120 ]. Although several natural and synthetic PPAR agonists have been studied in kidney-related disorders [ 46 , 122 , 123 , 124 ], whether PPAR modulators have protective actions against maternal-high-fat-diet-induced adverse renal outcomes in offspring is awaiting further elucidation.…”