The central theme of this program project is the regulation of apolipoprotein metabolism and its physiologic role in lipid and lipoprotein homeostasis. To achieve this goal, we organized a multi-disciplinary approach involving physiology, biochemistry, immunochemistry, and cell biology, employing both in vivo and in vitro techniques. We propose the following broad areas of investigation: 1. To study peripheral lymph lipoprotein metabolism by: a) further characterization of """"""""interstitial"""""""" lipoproteins; b) examining the biogenesis of lipoprotein particles found to be unique to peripheral lymph; c) defining the metabolic fate of the unique, discoidal """"""""interstitial"""""""" HDL particle; d) examining the production of apo A-IV-containing particles by the intestine and liver and their role in interstitial fluid; and e) studying the mechanism of the formation in the interstitial fluid of apo A-I unassociated with conventional lipoprotein particles. 2. To study in vivo modification of lipoproteins in the circulation by: a) examining the remodeling of """"""""interstitial"""""""" lipoproteins and determining the processes involved; b) studying the dynamics of lipoprotein remodeling (particularly apo A-IV particles and apo A-I unassociated with lipoproteins) in plasma and peripheral lymph; c) examining how remodeling of plasma and lymph lipoproteins (their apolipoprotein and lipid components) influences their metabolism; and d) determining how this remodeling may be involved in reverse cholesterol transport. 3. To study apoprotein synthesis by : a) defining the biogenesis and molecular structure of apo B; b) determining the physiologic importance of apo B phosphorylation with regard to VLDL assembly/secretion; and c) determining the genetic expression of apo B caused by physiologic """"""""effectors."""""""" We are also studying apolipoprotein synthesis by peripheral tissues, both in vivo in vitro. We believe these studies will contribute to our understanding of lipoprotein-apoprotein metabolism and its physiologic role in lipid homeostasis.
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