Liver metabolic alterations and changes in host intercompartmental metabolic correlation during progression of malaria

Abstract

¹H NMR-based metabonomics was used to investigate the multimodal response ofmice to malarial parasite infection by P. berghei ANKA. Liver metabolism was followed by NMR spectroscopy through the course of the disease in both male and female mice. Our results showed alterations in the level of several metabolites as a result of the infection. Metabolites like kynurenic acid, alanine, carnitine, and β-alanine showed significant alteration in the liver, suggesting altered kynurenic acid, glucose, fatty acid and amino acid pathways. Distinct sexual dimorphism was also observed in the global analysis of the liver metabolic profiles. Multiway principal component analysis (MPCA) was carried out on the liver, brain, and serum metabolic profile in order to explore the correlation of liver and brain metabolic profile to the metabolite profile of serum. Changes in such correlation profile also indicated distinct sexual dimorphism at the early stage of the disease. Indications are that the females are able to regulate their metabolism in the liver in such a way to maintain homeostasis in the blood. In males, however, choline in liver showed anticorrelation to choline content of serum indicating a higher phospholipid degradation process. The brain-serum correlation profile showed an altered energy metabolism in both the sexes. The differential organellar responses during disease progression have implications in malaria management.