Abstract
Weaning wields environmental, social, and nutritional stresses that are detectable in the blood metabolite levels of the offspring. Prenatal stress in the form of maternal immune activation (MIA) in response to infection, which is associated with health and behavior disorders, also elicits prolonged changes in blood and brain cytokine and metabolite levels of the offspring. The goal of this study was to investigate the effects of weaning and MIA on the offspring’s liver function to advance the understanding of the impact of stressors on peripheral and central nervous systems, physiology, and health. Gas chromatography–mass spectrometry analysis was used to compare the level of hepatic metabolites from 22-day-old pigs (n = 48) evenly distributed among weaning (nursed or weaned), viral MIA exposure (yes or no), and sexes. Weaning effects were detected on 38 metabolites at p-value < 0.05 (28 metabolites at FDR p-value < 0.05), and sex-dependent MIA effects were detected on 11 metabolites. Multiple intermediate and final products of the enriched (FDR p-value < 0.05) glycolysis and gluconeogenesis and pentose phosphate pathways were over-abundant in nursed relative to weaned pigs. The enriched pathways confirm the impact of weaning on hepatic metabolic shift, oxidative stress, and inflammation. Higher levels of the glucogenic amino acid histidine are observed in pigs exposed to MIA relative to controls, suggesting that the role of this metabolite in modulating inflammation may supersede the role of this amino acid as an energy source. The lower levels of cholesterol detected in MIA pigs are consistent with hypocholesterolemia profiles detected in individuals with MIA-related behavior disorders. Our findings underline the impact of weaning and MIA stressors on hepatic metabolites that can influence peripheral and central nervous system metabolic products associated with health and behavior disorders.
Highlights
The process of weaning exerts nutritional, physiological, environmental, and social stresses on the offspring (Campbell et al, 2013)
Our results indicate that the highest impact of weaning on hepatic gluconeogenesis metabolism occurs in the priming stage that culminates with fructose 1,6-bisphosphate (Harris and Harper, 2015)
Histidine is a precursor for histamine, and the histidine profile observed in the present study suggests chronic hepatic inflammatory priming due to maternal immune activation (MIA) (Moya-Garcia et al, 2005; Schneider et al, 2010)
Summary
The process of weaning exerts nutritional, physiological, environmental, and social stresses on the offspring (Campbell et al, 2013). Rodent and pig models demonstrate that shortly after weaning, the immune status of the offspring is low while transitioning from the passive immunity offered by the mother’s milk to developing individual active immunity. During this period, the offspring is susceptible to infection, can experience digestive problems due to the diet change, and must adapt to a new environment and possibly interactions with new pen or cage mates (Jayaraman and Nyachoti, 2017; Xiong et al, 2019). Glucose is processed into fat or glycogen and, through gluconeogenesis, these can be back-transformed into glucose in the liver. The liver filters toxins and chemicals from the blood and reprocesses hemoglobin
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