OVEREXPRESSION OF PERILIPIN-A AND PERILIPIN-B BLOCKS THE ABILITY OF TUMOR-NECROSIS-FACTOR-ALPHA TO INCREASE LIPOLYSIS IN 3T3-L1 ADIPOCYTES

Perilipins, a family of phosphoproteins, are specifically located at t he surface of intracellular lipid (triacylglycerol) droplets, the site of lipolysis. Stimulation of lipolysis in 3T3-L1 adipocytes by tumor necrosis factor alpha (TNF-alpha) is associated with a decrease in tot al cellular expression of perilipin A and B, consistent with the hypot hesis that a decrease in perilipin protein expression is required for TNF-alpha-induced lipolysis. Adenovirus-mediated overexpression of per ilipin A or B maintains perilipin protein levels on the lipid droplet and blocks TNF alpha-induced lipolysis. In contrast, overexpression of perilipin A or perilipin B does not inhibit isoproterenol-stimulated lipolysis and does not alter the isoproterenol-induced migration of pe rilipins from the lipid droplet. These results provide the first evide nce of how perilipin functions and suggest that TNF-alpha regulates li polysis, in part, by decreasing perilipin protein levels at the lipid droplet surface.