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Application of metabolomics to identify metabolite patterns showing the importance of dietary carbohydrate source in neonatal rats

University of British Columbia

Lactose is a glucose and galactose disaccharide and is found exclusively in mammalian milk. The evolution of lactose as a unique component of human milk (with 50% galactose) and its metabolic advantage in infants is poorly understood. There is also a limited understanding of the potential implications of clinical nutrition support using lactose-free nutrition, such as dextrose (glucose) as the sole carbohydrate source in intravenous nutrition and glucose-corn syrup solids (CSS) (100% glucose) in formula for infants. The liver takes up 90% of galactose. In contrast, the liver clears only 30% of glucose. Glucose stimulates release of insulin from the pancreas whereas galactose does not. The goal of my thesis was to use ‘metabolomics’, in a neonatal rat model of gastrostomy feeding, to differentiate metabolic effects in rat pups fed milk formula complete in protein, fat, minerals and vitamins, but with either lactose or CSS as the carbohydrate source. I hypothesize that galactose and specific metabolites of galactose metabolism will be differentiated between lactose-fed and CSS-fed rat pups by target compound analysis; and targeted metabolomics will highlight differences in metabolite patterns in hepatic metabolism from lactose or CSS feeding. Liver, plasma and urine samples were collected at 10 and 14 days after birth. Significant differences in galactose and galactonate levels were observed in the liver at day 10 and 14, with no differences glucose. Metabolites that were different between the groups were: D-Ribose, pyrimidine, glycine and malate in rat pups at day 10 and leucine and isoleucine at day 10 and 14, which were significantly higher in the lactose-fed group. The data obtained show that early dietary lactose has definitive effects on hepatic metabolites that can be mapped to pathways of carbohydrate, protein, and fat metabolism and are different to non-lactose carbohydrate feeding. My findings suggest that utilization of galactose, as a consistent source of glucose could prove beneficial for supply to glucose-dependent organs such as the rapidly developing infant brain. Advancing the use of metabolomics to enhance understanding of the impact of diet will provide an opportunity to improve health outcome for infants.

Text

2016-01-26

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/56699

Reproductive and Developmental Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/