The aim of this project is to examine the lipid clearing mechanism, the interaction between the enzymes and cofactors (apolipoproteins) regulating this process and the relationship between lipase(s) levels, exogenous (infused) lipid, heparin and endogenously synthesized triglycerides, (very low density lipoproteins VLDL) and cholesterol (lipoprotein-X). These studies will be carried out in premature, parenterally fed infants and in newborn animals, where not feasable in humans. Answers to the following questions will be sought: 1. What is the effect of lipid infusion on endothelial and tissue lipase levels (lipoprotein lipase-LPL, and hepatic lipase-HL)? 2. What is the effect of the type of lipid infused? 3. What is the effect of lipid infusion on the composition of aerum lipids? 4. What is the relationship between lipid infusion, the appearance of Lipoprotein-X (LP-X) and the activity of lecithin cholesterol acyl transferase (LCAT) in the circulation of very low birth weight (VLBW) infants? 5. What is the role of hepatic lipase in the process of lipid clearing in VLBW infants? These questions will be answered by studies of the endothelial and tissue lipases in newborn animals maintained on regimens similar to the ones employed in the management of parenterally fed preterm infants and by studies of the heparin releasable endothelial lipases: lipoprotein lipase (LPL) and hepatic lipase (HL), quantitated in serum as post heparin lipolytic activity - PHLA, in infants maintained on total parenteral nutrition in the intensive care nursery. Since VLBW infants are maintained exclusively on parenteral nutrition and receive lipid infusion for long periods, a better understanding of all aspects of the lipid clearing mechanism is necessary for the optimal management of these very premature infants. These studies are also leading to development of rapid and highly accurate non-invasive tests of the lipid clearing ability of preterm infants.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015631-09
Application #
3313199
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1982-07-01
Project End
1996-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Iverson, S J; Hamosh, M; Bowen, W D (1995) Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals. J Comp Physiol B 165:384-95
Goel, R; Hamosh, M; Stahl, G E et al. (1995) Plasma lecithin: cholesterol acyltransferase and plasma lipolytic activity in preterm infants given total parenteral nutrition with 10% or 20% Intralipid. Acta Paediatr 84:1060-4
Mao, J; Hamosh, M (1992) Postnatal development of plasma-lipid-clearing enzymes (lipoprotein lipase, hepatic lipase and lecithin:cholesterol acyl transferase) and lipid profiles in suckling rats. Biol Neonate 62:1-9
Spear, M L; Amr, S; Hamosh, M et al. (1991) Lecithin:cholesterol acyltransferase (LCAT) activity during lipid infusion in premature infants. J Pediatr Gastroenterol Nutr 13:72-6
Amr, S; Hamosh, P; Hamosh, M (1989) Effect of intralipid infusion on lecithin:cholesterol acyltransferase and lipoprotein lipase in young rats. Biochim Biophys Acta 1001:145-9
Spear, M L; Stahl, G E; Hamosh, M et al. (1988) Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions. J Pediatr 112:94-8
Papadopoulos, A; Hamosh, M; Chowdhry, P et al. (1988) Lecithin-cholesterol acyltransferase in newborn infants: low activity level in preterm infants. J Pediatr 113:896-8
Mehta, N R; Liao, T H; Hamosh, M et al. (1988) Effect of total parenteral nutrition on lipase activity in the stomach of very low birth weight infants. Biol Neonate 53:261-6
Amr, S; Chowdhry, P; Hamosh, P et al. (1988) Low levels of apolipoprotein A1 are not contributors to the low lecithin-cholesterol acyl transferase activity in premature newborn infants. Pediatr Res 24:191-3
Hamosh, M (1987) Lipid metabolism in premature infants. Biol Neonate 52 Suppl 1:50-64

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