C. Londos, D. L. Brasaemle, J. Gruia-Gray, D. A. Servetnick, C. J. Schultz, D. M. Levin, A. R. Kimmel

For several reasons it seems reasonable to suspect that perilipins participate in lipid hydrolysis. First, they are located at the lipid droplet surface, the presumed site of HSL and cholesteryl esterase action. Secondly, they are polyphosphorylated by PKA in concert with lipid hydrolysis. Finally, these proteins appear to be expressed primarily, if not solely, in adipocytes and steroidogenic cells, cells in which lipid hydrolysis is stimulated by cyclic AMP and mediated by HSL or cholesteryl esterase(s), whereas other cells that contain abundant neutral lipid depositions contain no perilipin [13]. Interestingly, these closely related hydrolases share no homology with other mammalian lipases [3]. Although such attributes provide a link between perilipin and lipid hydrolysis, we have no evidence that perilipins participate directly in, or are necessary for, lipid catabolism. The basis for the strong affinity between the perilipins and neutral lipids is unknown. Clearly, lipids and perilipins are tightly linked, as evidenced by selective targeting of epitope-tagged perilipin to lipid droplets and by the paradoxical appearance of lipid droplets in pre-adipocytes transfected with a sense perilipin A construct. Indeed, in differentiating adipocytes the earliest lipid depositions are associated with perilipins, and restriction of perilipin synthesis with anti-sense constructs may impede lipid formation and deposition. It remains to be determined if, in the normal course of events, perilipins are directed toward lipid depositions or if lipids are transported to perilipin foci. Whatever the temporal sequence, the result is that neutral lipids are encased in perilipin-bounded droplets.(ABSTRACT TRUNCATED AT 250 WORDS)