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

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Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice. / Fernandez, Celine; Schuhmann, Kai; Herzog, Ronny; Fielding, Barbara; Frayn, Keith; Shevchenko, Andrej; James, Peter; Holm, Cecilia; Ström, Kristoffer.

In: PLoS ONE, Vol. 6, No. 6, 2011.

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Fernandez, Celine ; Schuhmann, Kai ; Herzog, Ronny ; Fielding, Barbara ; Frayn, Keith ; Shevchenko, Andrej ; James, Peter ; Holm, Cecilia ; Ström, Kristoffer. / Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice. In: PLoS ONE. 2011 ; Vol. 6, No. 6.

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TY - JOUR

T1 - Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice

AU - Fernandez, Celine

AU - Schuhmann, Kai

AU - Herzog, Ronny

AU - Fielding, Barbara

AU - Frayn, Keith

AU - Shevchenko, Andrej

AU - James, Peter

AU - Holm, Cecilia

AU - Ström, Kristoffer

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0021603

DO - 10.1371/journal.pone.0021603

M3 - Article

C2 - 21738729

VL - 6

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

ER -