Dawn L. Brasaemle
Department of Nutritional Sciences
School of Environmental & Biological Sciences
96 Lipman Drive
New Brunswick, NJ 08901-0231
Biology of neutral lipid storage and release
We are particularly interested in the role that structural lipid droplet-associated proteins within the PAT (perilipin, adipophilin, TIP47) family of proteins play in forming an organizing scaffold that regulates the access of lipid metabolic enzymes to stored neutral lipids. Perilipins are a family of polyphosphorylated proteins coating the surfaces of lipid droplets in adipocytes and steroidogenic cells of the adrenal gland, testes, and ovaries. In adipocytes, perilipins are required to maintain fat stores by controlling the rates of triacylglycerol turnover and release. Adipophilin (also called ADRP) and TIP47 are structurally related to perilipins, but are found on lipid droplets in many cell types throughout the body. A major project in the laboratory uses approaches of biochemistry and molecular and cellular biology to investigate the structural basis for perilipin function in controlling lipid droplet morphology and triacylglycerol storage and hydrolysis.
Figure 1. SDS-PAGE gel of lipid droplet-associated proteins from basal (left) and lipolytically stimulated (right) 3T3-L1 adipocytes.
Figure 2. CGI-58 associates with lipid droplets through an interaction with perilipin A in basal 3T3-L1 adipocytes.
Using proteomics, we have identified CGI-58 as a major component of adipocyte lipid droplets (Figure 2). Mutations in CGI-58 are responsible for a rare inherited neutral lipid storage disorder in humans, suggesting that CGI-58 plays a critical role in triacylglycerol metabolism. A second major project in the laboratory uses a variety of technologies including in vitro studies of recombinant proteins, RNAi approaches in cultured mammalian cells, and the characterization of transgenic mice to investigate the function of CGI-58 in triacylglycerol metabolism.
Finally, we are interested in further identification of novel lipid droplet-associated proteins and in studying the functions of these proteins.