Overexpression of perilipin A and 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 the 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 total cellular expression of perilipin A and B, consistent with the hypothesis that a decrease in perilipin protein expression is required for TNF-alpha-induced lipolysis. Adenovirus-mediated overexpression of perilipin 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 perilipins from the lipid droplet. These results provide the first evidence of how perilipin functions and suggest that TNF-alpha regulates lipolysis, in part, by decreasing perilipin protein levels at the lipid droplet surface.
Souza
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Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and the Division of Endocrinology, Tupper Research Institute, New England Medical Center, Boston, Massachusetts 02111, USA.
de Vargas
L M
LM
Yamamoto
M T
MT
Lien
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P
Franciosa
M D
MD
Moss
L G
LG
Greenberg
A S
AS
D016475:3T3 Cells; D000256:Adenoviridae; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol