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Journal of Lipid Research, Vol. 48, 2547-2559, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology
Thematic Review |
Department of Nutritional Sciences and the Rutgers Center for Lipid Research, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901
Published, JLR Papers in Press, September 18, 2007.
1 To whom correspondence should be addressed. e-mail: brasaemle{at}aesop.rutgers.edu
The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the body, whereas cholesteryl ester-rich droplets of many other cells provide building materials for local membrane synthesis and repair. These lipid droplets are coated with one or more of five members of the perilipin family of proteins: adipophilin, TIP47, OXPAT/MLDP, S3-12, and perilipin. Members of this family share varying levels of sequence similarity, lipid droplet association, and functions in stabilizing lipid droplets. The most highly studied member of the family, perilipin, is the most abundant protein on the surfaces of adipocyte lipid droplets, and the major substrate for cAMP-dependent protein kinase [protein kinase A (PKA)] in lipolytically stimulated adipocytes. Perilipin serves important functions in the regulation of basal and hormonally stimulated lipolysis. Under basal conditions, perilipin restricts the access of cytosolic lipases to lipid droplets and thus promotes triacylglycerol storage. In times of energy deficit, perilipin is phosphorylated by PKA and facilitates maximal lipolysis by hormone-sensitive lipase and adipose triglyceride lipase. A model is discussed whereby perilipin serves as a dynamic scaffold to coordinate the access of enzymes to the lipid droplet in a manner that is responsive to the metabolic status of the adipocyte.
Supplementary key words adipophilin • adipose differentiation-related protein • TIP47 • hormone-sensitive lipase • adipose triglyceride lipase • triacylglycerol • cAMP-dependent protein kinase • adipocyte
Abbreviations: ATGL, adipose triglyceride lipase; MEF, mouse embryonic fibroblast; PKA, protein kinase A; TNF-
, tumor necrosis factor-
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