In humans, apolipoprotein E (apoE) deficiency causes hyperlipidemia and vascular disease. We have recently determined that harbor seals and sea lions do not have detectable levels of plasma apoE, yet they do not develop hyperlipidemia or remnant lipoproteins typically seen in apoE deficient humans. The diet of seals and sea lions is rich in omega-3 fatty acids and may suppress VLDL synthesis, thus """"""""masking"""""""" the impact of the apoE deficiency. The objectives of this study are 1) to determine the basis for the apoE deficiency in harbor seals and sea lions, 2) to determine the mechanism by which seals efficiently metabolize triglyceride-rich lipoproteins, and 3) to determine the role of dietary omega-3 fatty in maintaining normolipemia. First, we will determine which apoprotein(s) are responsible for receptor-mediated uptake of seal lipoproteins using both cell culture techniques and in vivo turnover studies. Second, experiments will be conducted to determine whether harbor seals and sea lions have the apoE gene and apoE mRNA using Southern and Northern blotting techniques. respectively. Third, we will assess the role of the fish-diet by feeding seals an alternative isocaloric diet high in cholesterol and saturated fat. These studies of lipoprotein metabolism are unique in that harbor seals and sea lions are animal models in which the full impact of apoE deficiency can be studied. Because their diets are composed entirely of fish, they offer a unique opportunity to determine the maximal effect of such a diet, especially in the face of apoE deficiency. Thus these studies are highly relevant to the goal of understanding the relationship of diet and lipoprotein metabolism to the causation of atherosclerosis in man.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039608-04
Application #
3356391
Study Section
Metabolism Study Section (MET)
Project Start
1990-04-01
Project End
1991-09-29
Budget Start
1990-09-30
Budget End
1991-09-29
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Davis, R W; Pierotti, V R; Lauer, S J et al. (1991) Lipoproteins in pinnipeds: analysis of a high molecular weight form of apolipoprotein E. J Lipid Res 32:1013-23