Browsing by Author "Hyde, Matthew J."

Background: Routine total parenteral nutrition (TPN) in neonatal care can result in hepatic dysfunction in 40–60% of patients, most commonly as fatty liver, but little work has been conducted on the underlying mechanisms causing hepatic dysfunction. Objective: To use a piglet model for the premature human neonate on TPN, supplemented with lipid emulsions, to investigate hepatic responses. Method: Piglets were delivered 2 days prematurely. Six control piglets were fed enterally (E), whilst twelve animals were maintained on TPN. TPN piglets received the standard TPN solution plus the lipid emulsion as either ClinOleic (C, n = 6) or Intralipid (I, n = 6). Hepatic lipid content and the fatty acid composition of liver triacylglyercol (TAG) as well as hepatic lipase (HL) activity were determined. Lipoprotein lipase (LPL) activity was measured in the liver, muscle and adipose tissue. The plasma concentrations of choline, bilirubin, TAG and non-esterified fatty acids (NEFA) were also measured. Results: Liver lipid was significantly increased in piglets on TPN and the tissue fatty acid profiles reflected the lipid emulsion. HL and LPL activities were reduced in liver but LPL increased in adipose tissue during TPN. Plasma concentrations of choline, bilirubin, TAG and NEFA were similar across the treatments. Conclusions: The results suggest fatty liver occurs in neonates receiving TPN and the source of the accumulated lipid appears to be the lipid emulsion used. The factors regulating lipase activity during TPN require further study. The piglet can be used as a model for neonatal TPN.

The multicomponent analysis of human breast milk (BM) by metabolic profiling is a new area of study applied to determining milk composition, and is capable of associating BM composition with maternal characteristics, and subsequent infant health outcomes. A multiplatform approach combining HPLC-MS and ultra-performance LC-MS, GC-MS, CE-MS, and 1H NMR spectroscopy was used to comprehensively characterize metabolic profiles from seventy BM samples. A total of 710 metabolites spanning multiple molecular classes were defined. The utility of the individual and combined analytical platforms was explored in relation to numbers of metabolites identified, as well as the reproducibility of the methods. The greatest number of metabolites was identified by the single phase HPLC-MS method, while CE-MS uniquely profiled amino acids in detail and NMR was the most reproducible, whereas GC-MS targeted volatile compounds and short chain fatty acids. Dynamic changes in BM composition were characterized over the first 3 months of lactation. Metabolites identified as altering in abundance over lactation included fucose, di- and triacylglycerols, and short chain fatty acids, known to be important for infant immunological, neurological, and gastrointestinal development, as well as being an important source of energy. This extensive metabolic coverage of the dynamic BM metabolome provides a baseline for investigating the impact of maternal characteristics, as well as establishing the impact of environmental and dietary factors on the composition of BM, with a focus on the downstream health consequences this may have for infants.