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Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.

Holm, Cecilia LU (2003) In Biochemical Society Transactions 31(Pt 6). p.1120-1124
Abstract
HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA... (More)
HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA site remains elusive. Adipocytes isolated from homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted catecholamine-induced glycerol release and reduced fatty acid release, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver, adipose tissue and skeletal muscle appear all to be sites of impaired insulin sensitivity in HSL-null mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adipose tissue, cholesteryl ester hydrolase, insulin resistance, perilipin, protein kinase A
in
Biochemical Society Transactions
volume
31
issue
Pt 6
pages
1120 - 1124
publisher
Biochemical Society
external identifiers
  • wos:000187289000004
  • pmid:14641008
  • scopus:0348049843
ISSN
0300-5127
language
English
LU publication?
yes
id
183d4c70-d3e4-43d2-b72e-a82a47a2be20 (old id 119896)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14641008&dopt=Abstract
date added to LUP
2007-07-13 11:39:20
date last changed
2018-02-18 03:35:42
@article{183d4c70-d3e4-43d2-b72e-a82a47a2be20,
  abstract     = {HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA site remains elusive. Adipocytes isolated from homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted catecholamine-induced glycerol release and reduced fatty acid release, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver, adipose tissue and skeletal muscle appear all to be sites of impaired insulin sensitivity in HSL-null mice.},
  author       = {Holm, Cecilia},
  issn         = {0300-5127},
  keyword      = {adipose tissue,cholesteryl ester hydrolase,insulin resistance,perilipin,protein kinase A},
  language     = {eng},
  number       = {Pt 6},
  pages        = {1120--1124},
  publisher    = {Biochemical Society},
  series       = {Biochemical Society Transactions},
  title        = {Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.},
  volume       = {31},
  year         = {2003},
}