Integrative Analysis of Liver Metabolomics and Transcriptomics Reveals Oxidative Stress in Piglets with Intrauterine Growth Restriction

SIMPLE SUMMARY: Although the correlation between oxidative stress and liver metabolic dysfunction has been established in piglets with intrauterine growth restriction, detailed information concerning the molecular mechanisms that facilitate this relationship remains limited. In the present study, metabolomic and transcriptomic techniques were used to investigate differences in gene expression and metabolites in the liver of piglets in intrauterine growth restriction and normal birth weight groups to systematically analyze the potential mechanism of metabolic characteristics induced by oxidative stress in the liver of intrauterine growth restriction piglets. Our results revealed that the intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver. ABSTRACT: The correlation between oxidative stress and liver metabolic dysfunction in piglets with intrauterine growth restriction (IUGR) remains limited. Therefore, the objective of the present study was to investigate potential mechanisms of metabolic characteristics induced by oxidative stress in the livers of IUGR piglets using metabolomic and transcriptomic analysis. Analysis of the phenotypic characteristics showed that the liver weight of the intrauterine growth restriction piglets was significantly lower than that of normal birth weight piglets. Intrauterine growth restriction piglets exhibited disordered hepatic cord arrangement and vacuolization as well as excessive lipid accumulation in hepatocytes. In addition, the activities of antioxidant enzymes were significantly decreased in the liver of the intrauterine growth restriction piglets, whereas the level of the lipid peroxidation marker MDA was significantly increased. Finally, our findings revealed that intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver. In summary, these data provided a detailed theoretical reference for revealing the hepatic metabolic characteristics of intrauterine growth restriction piglets.