Identification of novel protein targets regulated by maternal dietary fatty acid composition in neonatal rat liver

Abstract

Polyunsaturated fatty acids regulate metabolic pathways, which in early development could have important consequences to adaptation to extra-uterine life and programming of metabolic pathways. Female rats were fed one of two diets identical in all nutrients, except that the fat in one diet was high in unsaturated fatty acids (UFA) and the other low UFA, through gestation and lactation. Two-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis of protein extracts from 3-day old pup liver resolved over 800 proteins. Employing MALDI-TOF MS and peptide mapping we identified 11 proteins that differed more than three-fold between the groups, 10 up regulated and one down regulated in the high UFA group. The up-regulated proteins included fructose-1,6-bisphosphatase 1, glycerol-3-phosphate dehydrogenase, galactokinase 1, 40S ribosomal protein SA, elongation factor 1-gamma, protein disulfide-isomerase A6, catalase, cytokeratin-8 and 60 kDa heat shock protein, and the down-regulated protein was argininosuccinate synthase, none having been previously reported to be regulated by fatty acids in the developing liver. We further determined that fructose-1,6-biphosphatase is acetylated at the N-terminus. We demonstrate that early fatty acid nutrition impacts hepatic metabolic pathways relevant to gluconeogenesis, redox balance and nitric oxide signaling.