Carrier mediated lipid transport

Lipids are essential molecules for cellular function; they are required for energy production, membrane structure, and can serve as signaling molecules. Normal metabolism requires cellular uptake and efflux as well as intercellular transport of lipids. Disruption of these events can lead to pathological processes like obesity and atherosclerosis.; Transport of lipids between tissues involves moving hydrophobic species through a polar environment. This is achieved by carrier mediated lipid transport. These carriers can have significant impact on cellular uptake and efflux of lipids. This thesis investigated carrier mediated lipid transport in two situations, (1) long chain fatty acids (LCFAs) and the carrier protein albumin, and (2) cholesterol (and other lipids) carried by high density lipoprotein particles.; Significant issues regarding cellular LCFA uptake from albumin remain unresolved. (1) How do LCFAs traverse the plasma membrane, and (2) is an albumin receptor involved in LCFA uptake? With respect to the first question, we hypothesized that the mechanism of LCFA uptake may be sensitive to cellular cholesterol. Our studies concluded that cholesterol-depleting agents inhibit LCFA uptake but not that of a non-carrier mediated substrate. In regard to the second question, we investigated if albumin binding proteins exist on the cell surface of adipocytes. We found that albumin binding activity increased as cells undergo adipogenesis, and candidate proteins for this activity were found.; We also investigated the role of the high density lipoprotein (HDL) receptor, scavenger receptor class B type I (SR-BI) in cholesterol metabolism and atherosclerosis. SR-BI has been found to be atheroprotective in mice, and this may involve cholesterol efflux from macrophage foam cells to HDL. We investigated the affect of bone marrow specific ablation of SR-BI on atherosclerosis in mice. We concluded that SR-BI expression in bone marrow-derived cells can protect against atherosclerosis in the absence of any changes in overall lipoprotein metabolism.