Hippocampal Phosphatidylcholine Stearic Acid Mediates the Relationship Between Serum Triacylglycerol Eicosanoic Acid and Hippocampal myo‐Inositol in the Young Pig
Authors: Mudd Austin T , Waworuntu Rosaline V , Berg Brian M , Donovan Sharon M , Dilger Ryan N 
Published: November 2023

In pediatric nutrition, there is increasing interest in identifying lipid fractions and specific fatty acids (FA) that are important for neonatal development. Throughout infancy, brain growth is highly dynamic and requires particular FA to ensure a proper developmental trajectory. Previous research has focused on the relationship between serum and brain FA. However, the relationship between neurodevelopmental markers and FA found in serum and brain has yet to be explored. A better understanding of these relationships may allow researchers to identify novel mechanisms of brain development. Thus, the objective of this exploratory study was to determine the relationship between serum FA, brain FA, and magnetic resonance imaging (MRI) measures of neurodevelopment in neonatal piglets. Beginning at 2 d and continuing until 30 d of age, 24 vaginally‐derived male piglets were provided custom milk replacer formulated to meet piglet nutrient requirements. At 30 d of age, piglets underwent magnetic resonance spectroscopy (MRS) procedures to quantify metabolite concentrations in the hippocampus. Following MRS, the right hippocampus and serum were harvested from pigs at 31 d of age for lipidomic profiling. Linear regressions were used to assess the relationship between serum FA and hippocampal MRS metabolites, as well as between serum FA and hippocampal FA. Subsequently, a mediation model was used for serum FA that significantly related to both hippocampal FA and hippocampal MRS metabolites. A bootstrapping method drawing 5,000 samples with replacement from the dataset was implemented to estimate a sampling distribution (95% confidence interval) for the indirect and direct mediation effects. The mediation analysis revealed that hippocampal phosphatidylcholine stearic acid (PC‐18:0) fully mediated the relationship between serum triacylglycerol eicosanoic acid (TG‐20:0) and hippocampal myo‐inositol (MI) concentrations. First, increased serum TG‐20:0 levels were related to increased levels of hippocampal PC‐18:0 (P = 0.002). Second, increased serum TG‐20:0 levels were related to decreased concentrations of hippocampal MI (P = 0.016). The indirect mediation path (i.e., effect of serum TG‐20:0 levels on hippocampal MI concentration through hippocampal PC‐18:0 levels) was also significant (P < 0.05; 95% CI: −2.15 – −0.18). The direct mediation pathway (i.e., effect of serum TG‐20:0 on hippocampal MI concentration, accounting for hippocampal PC‐18:0) was not significant (P > 0.05; 95% CI: −1.84 – 0.69). Thus, hippocampal PC‐18:0 levels fully mediated the relationship between serum TG‐20:0 and hippocampal MI. Previous research suggests brain phospholipid levels rise and MI concentrations decline early in life. This study is the first to link these two observations, while also offering a possible relationship whereby a specific serum fatty acid may be involved. Future work should focus on testing direct relationships between serum TG‐20:0 and hippocampal PC‐18:0.Support or Funding InformationThis project was funded by Mead Johnson Nutrition.