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Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice
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@MISC{Fern_altereddesaturation,
author = {Céline Fern and Kai Schuhmann and Ronny Herzog and Barbara Fielding and Keith Frayn and Peter James and Cecilia Holm and Kristoffer Ström},
title = {Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice},
year = {}
}
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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,
Keyphrases
hsl null mouse fatty acid hormone-sensitive lipase null mouse altered desaturation mrna level lipid profile high fat diet important role catecholamine-stimulated hydrolysis lowered ratio methodology principal finding expression profiling broad substrate specificity multifunctional enzyme retinyl ester altered expression lipoidal ester hsl deficiency targeted lipidomics fatty acid mobilization altered lipid profile cholesteryl ester adipose tissue stearoyl-coa desaturase white adipose tissue elovl1 elongase diet-induced obesity recently-suggested lipokine stored lipid normal lipid metabolism hormone-sensitive lipase
