Apo A2, C1 and C2 and Diet in human apoB Metabolism

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Apolipoproteins A2, C1, and C2, are constituents of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL), termed "apoB lipoproteins". Animal models and cell studies suggest substantial roles for apoA2, C1 and C2 as modulators of lipolysis and clearance of apoB lipoproteins from plasma. ApoA2 and apoC1 have properties that impair either lipolysis of VLDL or its uptake and clearance from plasma by receptors on the liver and other tissues, or both processes. In contrast to the substantial body of knowledge about apoE and C3, other components of apoB lipoproteins, virtually nothing is known about how apoA2, C1 and C2 affect the metabolism of apoB lipoproteins in humans. We propose to use tracer methodology using endogenous labeling with stable isotopes to uncover the metabolic pathways related to apoA2, C1 and C2 on apoB lipoproteins. Normal and mildly hypertriglyceridemic persons were given diets composed of foods that provided healthy 20 percent fat or 37 percent, mainly unsaturated fat diets. After 3 weeks on each diet, their apoB lipoprotein metabolism was traced by intravenous infusion of deuterated amino acids, with the subjects in the fasting state and again during intake of frequent small meals to establish a postprandial steady state. Lipoproteins will be prepared, using immunoaffinity chromatography and ultracentrifugation, from samples already collected. The proposed study will determine to what extent apoA2, C1 and C2 in apoB lipoproteins influence the establishment of the hypertriglyceridemic state, control the postprandial response to common diets, and mediate the effects of low-fat vs moderate unsaturated fat intake on apoB lipoprotein concentrations, established risk factors for coronary heart disease.