It has been proposed that subjects with a partial deficiency of lipoprotein lipase (LpL) are more likely to develop premature coronary artery disease because they are predisposed to the expression of combined lipoprotein phenotypes. To elucidate the metabolic consequences of reduced LpL function, the production and catabolic rates of apoB-100 (LDL, IDL and VLDL), and apoB48 (chylomicrons/remnants) will be determined by the endogenous labeling, deuterated leucine technique in 15 LPL deficient heterozygotes. Bolus 13C-leucine will be administered simultaneously to clarify clearance rates. These results will be compared to historical controls (n=22). A pilot study using the same method will be performed on 3 Type I, LpL deficient subjects. They will be studied in the continuously fed state after dietary stabilization is achieved on an average American diet over a 4 week period. Lipoprotein composition including lipids and apolipoproteins (SDS-PAGE and ELISA assays) will be determined. Lipoprotein particle size will be determined by gradient gel electrophoresis. By performing these analyses, we hope to address the following issues: 1. Is the processing of VLDL to IDL to LDL compromised in LpL deficient subjects? 2. Is the production of apoB100 increased in LpL deficient heterozygotes compared to normal controls? 3. Does apoB48 catabolism diminish in LpL deficient subjects?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL047496-02
Application #
2223712
Study Section
Nutrition Study Section (NTN)
Project Start
1993-12-10
Project End
1996-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Ooi, Esther M M; Russell, Betsy S; Olson, Eric et al. (2012) Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations. Arterioscler Thromb Vasc Biol 32:459-66