Metabolic development in the liver and the implications of the n-3 fatty acid supply.

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism.

Dietary lipid quality and long-term outcome.

Understanding the importance of dietary fat has grown beyond energy metabolism to recognition of the complex roles of fatty acids, particularly the ω-6 and ω-3 fatty acids in membrane lipids, inter- and intracellular communication and in regulating gene expression. The ω-6 and ω-3 fatty acids accumulated in developing tissues depend on the fatty acids transported across the placenta and secreted in breast milk. These in turn are dependent on maternal fatty acid intakes, which have changed dramatically in the past century with current western diets high in ω-6 linoleic acid and low in ω-3 fatty acids.

Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism.

Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver.

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

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.

High dietary omega-6 fatty acids contribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth.

Docosahexaenoic acid (DHA, 22:6omega-3) is a major polyunsaturated fatty acid in the brain and is required in large amounts during development. Low levels of DHA in the brain are associated with functional deficits. The omega-3 fatty acids are essential nutrients and their metabolism and incorporation in developing brain depends on the composition of dietary fat.

Relationship of dimethylglycine, choline, and betaine with oxoproline in plasma of pregnant women and their newborn infants.

Choline and glycine are inter-related through their roles in methyl metabolism. Choline is metabolized to betaine, which donates a methyl group to homocysteine to form methionine, also generating dimethylglycine, which is further metabolized to glycine. Choline is transported across the placenta and is higher in fetal than maternal plasma.

Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 alpha-linolenic acid ratios in normal, fat-fed pigs.

Although dietary fat has been associated with inflammation and cardiovascular diseases (CVD), most studies have focused on individuals with preexisting diseases. However, the role of dietary fatty acids on inflammatory pathways before the onset of any abnormality may be more relevant for identifying initiating factors and interventions for CVD prevention. We fed young male pigs one of three diets differing in n-6 and n-3 polyunsaturated fatty acids (PUFA) linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) for 30 days.