Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover.
Although neutral lipid storage droplets are ubiquitous in eukaryotic cells, very little is known about how their synthesis and turnover are controlled. Adipocyte differentiation-related protein (ADRP; also known as adipophilin) is found on the surface of lipid droplets in most mammalian cell types. To learn how ADRP affects lipid storage, we stably expressed the protein in human embryonic kidney 293 (HEK 293) cells, which express little endogenous ADRP. As expected, ADRP was targeted to the surface of lipid droplets and caused an increase in triacylglycerol (TAG) mass under both basal and oleate-supplemented conditions. At least part of the increased mass resulted from a 50% decrease in the rate of TAG hydrolysis in ADRP-expressing cells. Furthermore, ADRP expression increased the fraction of total cellular TAG that was stored in lipid droplets. ADRP expression induced a striking decrease in the association of adipose triglyceride lipase (ATGL) and mannose-6-phosphate receptor tail-interacting protein of 47 kDa with lipid droplets and also decreased the lipid droplet association of several other unknown proteins. Transient expression of ADRP in two other cell lines also reduced the lipid droplet association of catalytically inactive ATGL. We conclude that the reduced lipid droplet association of ATGL and/or other lipases may explain the decrease in TAG turnover observed in ADRP-expressing HEK 293 cells.
Listenberger
Laura L
LL
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
Ostermeyer-Fay
Anne G
AG
Goldberg
Elysa B
EB
Brown
William J
WJ
Brown
Deborah A
DA
D000818:Animals; D006224:Cricetinae; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D000070780:Perilipin-2; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
D008049:Lipase; D008565:Membrane Proteins; D000070780:Perilipin-2; D014280:Triglycerides; C000602982:PLIN2 protein, human; C000602983:Plin2 protein, mouse; C494794:PNPLA2 protein, human; D000217:Acyltransferases