Chylomicrons and very low density lipoproteins (VLDL) transport triacylglycerol in the blood stream. They are composed of a core of mostly triacylglycerol surrounded by a lipid-protein monolayer. The structual protein of chylomicrons and VLDL is apolipoprotein B (apoB). ApoB is also found in low density lipoproteins (LDL), a metabolic derivative of chylomicrons and VLDL. Clinical findings indicate that LDL may be involved in the development of coronary arteriosclerosis. We have used the rat to study the synthesis and metabolism of apoB. ApoB exists in the rat in three forms, B-100, B-95 and B- 48. Mr of B-48 is around 240,000 about one-half that of B-100 and B-95. We showed earlier that rat liver synthesizes all forms of apoB, whereas the intestines synthesizes only B-48. In vivo studies showed that B-48 is cleared from blood much faster than the other forms. Other findings indicated that B-95 and B-100 are incorporated into different populations of hepatic VLDL. Thus, the metabolic fate of VLDL, and possibly LDL, could be determined by the form of apoB present in the lipoprotein. We have developed a method for measuring in vivo, in the rat, incorporation of (3H) leucine into individual forms of apoB. The method is based on the ability of Triton WR-1339 to block clearance of all forms of apoB from the blood stream. Glucose infusion increased, and fasting decreased, the ratio of B-48 to the larger forms in VLDL without affecting the ratio of B-100 to B- 95. Surgical stress and Triton injection, in contrast, lowered the ratio of B-100 to B-95 without affecting the ratio of B-48 to the larger forms. These findings suggest that synthesis of each form of apoB is regulated individually by hormonal/nutritional factors.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
1987
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
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Country
United States
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