Proteomic, metabolomic and lipidomic approaches to unravel the roles of polyunsaturated fatty acid nutrition in the developing liver

Abstract

Polyunsaturated fatty acids (PUFA) regulate metabolism in adult liver; PUFA accumulation in fetal and infant liver depends on diet. We used combined proteomics, metabolomics and lipidomics to address whether PUFA nutrition impacts metabolic development in neonatal rat liver. Rats were fed as % energy, 3.9% 18:2n‐6 and 1.5% 18:3n‐3 (high PUFA), or 1 % 18:2n‐6 and <0.1% 18:3n‐3 (low PUFA) in gestation and lactation. On day 3 postnatal, lipidomics using HPLC and GLC showed lower n‐3/n‐6 PUFA, but no difference in lipid classes in low compared to high PUFA offspring. Liver proteins were resolved on 2D gels, resolving over 800 proteins. PDQuest analysis showed 24 proteins up‐regulated and 1 down‐regulated over 3 fold in the high compared to low PUFA group, and these were identified by MALDI‐TOF MS. Up‐regulated proteins included F‐1,6‐biphosphatase 1, G‐3‐P dehydrogenase, galactokinase 1, catalase and 60 kDa heat shock protein, with argininosuccinate synthase down‐regulated. GC‐MS profiling of small molecules in liver extracts, with principal component analysis to address changes in flux through metabolic pathways showed higher gluconeogenic amino acids in the high PUFA group. Finally, integration of results from the proteomic and metabolomic analyses into metabolic pathways shows that maternal lipid nutrition impacts pathways of gluconeogenesis and oxidative stress in developing liver. Funded by CIHRGrant Funding SourceMichael Smith Fdn Health Research Studentship