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Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice

Fernandez, Celine LU ; Schuhmann, Kai; Herzog, Ronny; Fielding, Barbara; Frayn, Keith; Shevchenko, Andrej; James, Peter LU ; Holm, Cecilia LU and Ström, Kristoffer LU (2011) In PLoS ONE 6(6).
Abstract
Background: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored lipids, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. The aim of this study was to define lipid profiles in plasma, white adipose tissue (WAT) and liver of HSL null mice, in order to better understand the role of this multifunctional enzyme. Methodology/ Principal Findings: This study used global and targeted lipidomics and expression... (More)
Background: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored lipids, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. The aim of this study was to define lipid profiles in plasma, white adipose tissue (WAT) and liver of HSL null mice, in order to better understand the role of this multifunctional enzyme. Methodology/ Principal Findings: This study used global and targeted lipidomics and expression profiling to reveal changed lipid profiles in WAT, liver and plasma as well as altered expression of desaturases and elongases in WAT and liver of HSL null mice on high fat diet. Decreased mRNA levels of stearoyl-CoA desaturase 1 and 2 in WAT were consistent with a lowered ratio of 16:1n7/16:0 and 18:1n9/18:0 in WAT and plasma. In WAT, increased ratio of 18:0/16:0 could be linked to elevated mRNA levels of the Elovl1 elongase. Conclusions: This study illustrates the importance of HSL for normal lipid metabolism in response to a high fat diet. HSL deficiency greatly influences the expression of elongases and desaturases, resulting in altered lipid profiles in WAT, liver and plasma. Finally, altered proportions of palmitoleate, a recently-suggested lipokine, in tissue and plasma of HSL null mice, could be an important factor mediating and contributing to the changed lipid profile, and possibly also to the decreased insulin sensitivity seen in HSL null mice. (Less)
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author
organization
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Contribution to journal
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published
subject
in
PLoS ONE
volume
6
issue
6
publisher
Public Library of Science
external identifiers
  • wos:000292290100044
  • pmid:21738729
  • scopus:79959652916
ISSN
1932-6203
DOI
10.1371/journal.pone.0021603
language
English
LU publication?
yes
id
271704e3-31a1-426a-b479-5750372d1bb9 (old id 2029173)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21738729?dopt=Abstract
date added to LUP
2011-07-27 14:23:28
date last changed
2017-11-05 03:55:11
@article{271704e3-31a1-426a-b479-5750372d1bb9,
  abstract     = {Background: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored lipids, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. The aim of this study was to define lipid profiles in plasma, white adipose tissue (WAT) and liver of HSL null mice, in order to better understand the role of this multifunctional enzyme. Methodology/ Principal Findings: This study used global and targeted lipidomics and expression profiling to reveal changed lipid profiles in WAT, liver and plasma as well as altered expression of desaturases and elongases in WAT and liver of HSL null mice on high fat diet. Decreased mRNA levels of stearoyl-CoA desaturase 1 and 2 in WAT were consistent with a lowered ratio of 16:1n7/16:0 and 18:1n9/18:0 in WAT and plasma. In WAT, increased ratio of 18:0/16:0 could be linked to elevated mRNA levels of the Elovl1 elongase. Conclusions: This study illustrates the importance of HSL for normal lipid metabolism in response to a high fat diet. HSL deficiency greatly influences the expression of elongases and desaturases, resulting in altered lipid profiles in WAT, liver and plasma. Finally, altered proportions of palmitoleate, a recently-suggested lipokine, in tissue and plasma of HSL null mice, could be an important factor mediating and contributing to the changed lipid profile, and possibly also to the decreased insulin sensitivity seen in HSL null mice.},
  author       = {Fernandez, Celine and Schuhmann, Kai and Herzog, Ronny and Fielding, Barbara and Frayn, Keith and Shevchenko, Andrej and James, Peter and Holm, Cecilia and Ström, Kristoffer},
  issn         = {1932-6203},
  language     = {eng},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice},
  url          = {http://dx.doi.org/10.1371/journal.pone.0021603},
  volume       = {6},
  year         = {2011},
}