In this application, we propose to study several aspects of intestinal lipoprotein metabolism. First, we will evaluate to in depth the role of the various parts of the intestine in the degradation of low density lipoprotein (LDL). A unique aspect of this work will be the use of antireceptor antibodies to study LDL metabolism. The distribution of receptors along the GI tract will be determined by immunohistochemistry and direct binding. The presence of receptors in crypt and villous cells and the subcellular location of the receptors will also be determined. Regulation of receptor number under the influence of altered serum level and dietary and pharmacologic perturbation will be studied as well as the effect of malignant degeneration on receptor number. In other studies, the role of the LDL receptor in high density lipoprotein metabolism will be studied. The question of whether there is transport of cholesterol in excess of apoprotein will be addressed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036659-02
Application #
3235141
Study Section
Metabolism Study Section (MET)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301
Fong, L G; Fujishima, S E; Komaromy, M C et al. (1995) Location and regulation of low-density lipoprotein receptors in intestinal epithelium. Am J Physiol 269:G60-72
Kraemer, F B; Sather, S A; Park, B et al. (1994) Low density lipoprotein receptors in rat adipose cells: subcellular localization and regulation by insulin. J Lipid Res 35:1760-72
Jackson, S M; Wood, L C; Lauer, S et al. (1992) Effect of cutaneous permeability barrier disruption on HMG-CoA reductase, LDL receptor, and apolipoprotein E mRNA levels in the epidermis of hairless mice. J Lipid Res 33:1307-14
Ellsworth, J L; Chandrasekaran, C; Cooper, A D (1991) Evidence for sterol-independent regulation of low-density lipoprotein receptor activity in Hep-G2 cells. Biochem J 279 ( Pt 1):175-87
Fong, L G; Fong, T A; Cooper, A D (1991) Inhibition of lipopolysaccharide-induced interleukin-1 beta mRNA expression in mouse macrophages by oxidized low density lipoprotein. J Lipid Res 32:1899-910
Choi, S Y; Fong, L G; Kirven, M J et al. (1991) Use of an anti-low density lipoprotein receptor antibody to quantify the role of the LDL receptor in the removal of chylomicron remnants in the mouse in vivo. J Clin Invest 88:1173-81
May, K; Kraemer, F B; Chen, J et al. (1990) ELISA measurement of LDL receptors. J Lipid Res 31:1683-91
Fong, L G; Fong, T A; Cooper, A D (1990) Inhibition of mouse macrophage degradation of acetyl-low density lipoprotein by interferon-gamma. J Biol Chem 265:11751-60
Fong, L G; Bonney, E; Kosek, J C et al. (1989) Immunohistochemical localization of low density lipoprotein receptors in adrenal gland, liver, and intestine. J Clin Invest 84:847-56