The transfer of cholesteryl ester and triglyceride between lipoproteins is an important component of lipoprotein metabolism in humans. These lipid transfers are mediated by cholesteryl ester transfer protein (CETP). CETP directly affects the levels of low density (LDL) and high density lipoprotein. Exactly how these lipid movements influence lipoprotein metabolism and control lipoprotein levels is an area of continuing investigation in our laboratory. Currently we are characterizing a novel protein in human plasma, designated LTIP or apolipoprotein F, which suppresses CETP activity. LTIP, lipid transfer inhibitor protein, is not simply a general inhibitor of CETP activity, but it preferentially blocks CETP-mediated lipid transfers involving LDL. Therefore, LTIP plays a key role in defining the lipid transfer events that CETP can mediate in plasma. We believe that the activity of this protein controls whether the actions of CETP are beneficial or harmful, and consequently whether CETP facilitates or impedes the development of atherosclerosis.
A second major focus of the lab investigates the role of CETP inside of cells. Cells contain both the secreted form of CETP and a smaller alternatively spliced variant. We have shown that adipocytes deficient in CETP have impaired ability to store lipids, and this disruption has widespread consequences on cellular lipid metabolism and cellular function. We are investigating the role of CETP in lipid transport between cellular organelles, its role in lipid droplet formation and its involvement in the assembly of lipoproteins, and the importance of the CETP splice variant in regulating these processes.
Research in the Morton lab focuses on understanding the mechanisms by which lipids (fats) are transported in the blood stream and inside of cells. Lipids, by definition, are not soluble in water-containing environments, so special mechanisms are needed to transport them inside of the body. Our lab studies a protein called cholesteryl ester transfer protein (CETP). Our past and currents studies show that CETP has a major role in transporting specific types of lipids in the blood stream and inside of cells. In blood, CETP plays a central in defining the levels of low density and high density lipoproteins, which are also known as "bad" and "good" cholesterol. Because of this function, CETP helps regulate a process by which the body gets rid of excess cholesterol. Inside cells, we believe that CETP transports lipids from the place in the cell where they are made to lipid droplets – storage depots for excess lipid. Lipid droplets are common in many cells and especially important in fat (adipose) tissue. Our laboratory investigates how, at the molecular level, CETP performs these important functions, and mechanisms that control the biological activity of CETP. We believe understanding these processes will provide novel insights into the factors that contribute to the development of heart disease and obesity.
Driscoll, Donna M., Ph.D., Department of Cell Biology, CCF
Kinter, Michael T., Ph.D., Department of Cell Biology, CCF
Izem, L, Morton, RE. Possible role for intracellular cholesteryl ester transfer protein in adipocyte lipid metabolism and storage. J. Biol. Chem. 282: 21856-21865, 2007
Morton, RE, Gnizak, H, Greene, DJ, Cho, K-H, Paromov, VM. Lipid transfer inhibitor protein (Apolipoprotein F) concentration in normolipidemic and hyperlipidemic subjects. J. Lipid Res. 49:127-135, 2008.
He, Y, Greene, DJ, Kinter, M, Morton, RE. Control of cholesteryl ester transfer protein activity by sequestration of lipid transfer inhibitor protein in an inactive complex. J. Lipid Res. 49:1529-1537, 2008.
Izem, L., Morton, RE. Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia. J. Lipid Res. 50: 676-684, 2009.
Morton, RE, Greene, DJ. Conversion of lipid transfer inhibitor protein (apolipoprotein F) to its active form depends on LDL composition. J. Lipid Res, 52: 2262-2271, 2011.