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.

Keywords: AMP-activated protein kinase (AMPK); asymmetric dimethylarginine; developmental origins of health and disease (DOHaD); hypertension; nutrient-sensing signal; short chain fatty acid; trimethylamine-N-oxide; uremic toxin.

Figure 1

Schematic diagram highlighting the various nutrient-sensing signals in pregnancy that may impact fetal programming resulting in hypertension in later life. These signals cover AMP-activated protein kinase (AMPK), peroxisome-proliferator activated receptors (PPARs), the mechanistic target of rapamycin (mTOR), and G-coupled protein receptors (GPRs).

Figure 2

Illustration of dysregulated nutrient-sensing signal interconnected with other molecular mechanisms related to developmental programming of hypertension. AMPK = AMP-activated protein kinase (AMPK); PPAR = peroxisome-proliferator activated receptor; mTOR = the mechanistic target of rapamycin (mTOR); GPRs = G-coupled protein receptors; NO = nitric oxide; RAS = renin-angiotensin system.

Figure 3

Schematic representation of the interrelationships between disturbed metabolism in pregnancy, developmental programming of hypertension, and reprogramming strategies.