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Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation

Sztalryd, C; Xu, GH; Dorward, H; Tansey, JT; Contreras, Juan Antonio LU ; Kimmel, AR and Londos, C (2003) In Journal of Cell Biology 161(6). p.1093-1103
Abstract
A key step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from Wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the p-adrenergic receptor-adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in pefilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the... (More)
A key step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from Wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the p-adrenergic receptor-adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in pefilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the nonadipocyte Chinese hamster ovary cell line by introduction of GFP-tagged HSL with and without perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid droplets only in cells that express fully phosphory-latable perilipin A, confirming that perilipin is required to elicit the HSL translocation reaction. Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A, these two proteins cooperate to produce a more rapidly accelerated lipolysis than do cells that express either of these proteins alone, indicating that lipolysis is a concerted reaction mediated by both protein kinase A-phosphorylated HSL and perilipin A. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adipocytes, ADRP/adipophilin, lipolysis, lipid storage droplets, HSL
in
Journal of Cell Biology
volume
161
issue
6
pages
1093 - 1103
publisher
Rockefeller University Press
external identifiers
  • wos:000183827400010
  • pmid:12810697
  • scopus:0037477829
ISSN
0021-9525
DOI
language
English
LU publication?
yes
id
57af705f-cb92-43ad-b3c3-0d37182d18f5 (old id 307206)
date added to LUP
2007-09-23 10:03:56
date last changed
2018-06-17 04:02:17
@article{57af705f-cb92-43ad-b3c3-0d37182d18f5,
  abstract     = {A key step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from Wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the p-adrenergic receptor-adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in pefilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the nonadipocyte Chinese hamster ovary cell line by introduction of GFP-tagged HSL with and without perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid droplets only in cells that express fully phosphory-latable perilipin A, confirming that perilipin is required to elicit the HSL translocation reaction. Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A, these two proteins cooperate to produce a more rapidly accelerated lipolysis than do cells that express either of these proteins alone, indicating that lipolysis is a concerted reaction mediated by both protein kinase A-phosphorylated HSL and perilipin A.},
  author       = {Sztalryd, C and Xu, GH and Dorward, H and Tansey, JT and Contreras, Juan Antonio and Kimmel, AR and Londos, C},
  issn         = {0021-9525},
  keyword      = {adipocytes,ADRP/adipophilin,lipolysis,lipid storage droplets,HSL},
  language     = {eng},
  number       = {6},
  pages        = {1093--1103},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation},
  url          = {http://dx.doi.org/},
  volume       = {161},
  year         = {2003},
}