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

Author:
  • Celine Fernandez
  • Kai Schuhmann
  • Ronny Herzog
  • Barbara Fielding
  • Keith Frayn
  • Andrej Shevchenko
  • Peter James
  • Cecilia Holm
  • Kristoffer Ström
Publishing year: 2011
Language: English
Publication/Series: PLoS ONE
Volume: 6
Issue: 6
Document type: Journal article
Publisher: Public Library of Science

Abstract english

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.

Keywords

  • Cardiac and Cardiovascular Systems
  • Endocrinology and Diabetes

Other

Published
  • Molecular Endocrinology
  • Hypertension and Cardiovascular Disease
  • ISSN: 1932-6203
Peter James
E-mail: peter [dot] james [at] immun [dot] lth [dot] se

Professor

Department of Immunotechnology

+46 46 222 14 96

+46 70 247 79 60

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