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J. Biol. Chem., Vol. 275, Issue 49, 38486-38493, December 8, 2000
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From the The perilipins are the most abundant proteins at
the surfaces of lipid droplets in adipocytes and are also found in
steroidogenic cells. To investigate perilipin function, perilipin A,
the predominant isoform, was ectopically expressed in fibroblastic
3T3-L1 pre-adipocytes that normally lack the perilipins. In control
cells, fluorescent staining of neutral lipids with Bodipy 493/503
showed a few minute and widely dispersed lipid droplets, while in cells
stably expressing perilipin A, the lipid droplets were more numerous
and tightly clustered in one or two regions of the cytoplasm.
Immunofluorescence microscopy revealed that the ectopic perilipin A
localized to the surfaces of the tiny clustered lipid droplets;
subcellular fractionation of the cells using sucrose gradients
confirmed that the perilipin A localized exclusively to lipid droplets.
Cells expressing perilipin A stored 6-30-fold more triacylglycerol
than control cells due to reduced lipolysis of triacylglycerol stores. The lipolysis of stored triacylglycerol was 5 times slower in lipid-loaded cells expressing perilipin A than in lipid-loaded control
cells, when triacylglycerol synthesis was blocked with 6 µM triacsin C. This stabilization of
triacylglycerol was not due to the suppression of triacylglycerol
lipase activity by the expression of perilipin A. We conclude that
perilipin A increases the triacylglycerol content of cells by forming a
barrier that reduces the access of soluble lipases to stored
lipids, thus inhibiting triacylglycerol hydrolysis. These studies
suggest that perilipin A plays a major role in the regulation of
triacylglycerol storage and lipolysis in adipocytes.
Perilipin A Increases Triacylglycerol Storage by Decreasing the
Rate of Triacylglycerol Hydrolysis*
§¶,§,
**,, and
Department of Biochemistry, MCP Hahnemann
University, Philadelphia, Pennsylvania 19129, the
§ Department of Nutritional Sciences, Rutgers, The State
University of New Jersey, New Brunswick, New Jersey 08901, and the
Molecular Mechanisms of Development Section and
Membrane Regulation Section, Laboratory of
Cellular and Developmental Biology, NIDDK, National Institutes of
Health, Bethesda, Maryland 20892
*
This work was supported by American Heart
Association-Southeastern Pennsylvania Affiliate Grant B98429E (to
D. L. B.) and an American Diabetes Association research grant
(to D. L. B.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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