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Journal of Lipid Research, Vol. 44, 154-163, January 2003
Copyright © 2003 by Lipid Research, Inc.

Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis

Stéphanie Lucas, Geneviève Tavernier, Claire Tiraby, Aline Mairal and Dominique Langin¹

INSERM U317, Institut Louis Bugnard, Centre Hospitalier Universitaire de Rangueil, Université Paul Sabatier, 31403 Toulouse Cedex 4, France

¹ To whom correspondence should be addressed. e-mail: langin{at}toulouse.inserm.fr

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters (CEs). The enzyme is highly expressed in adipose tissues (ATs), where it is thought to play an important role in fat mobilization. The purpose of the present work was to study the effect of a physiological increase of HSL expression in vivo. Transgenic mice were produced with a 21 kb human genomic fragment encompassing the exons encoding the adipocyte form of HSL. hHSL mRNA was expressed at 3-fold higher levels than murine HSL mRNA in white adipocytes. Transgene expression was also observed in brown adipose tissue (BAT) and skeletal muscle. The human protein was detected in ATs of transgenic (Tg) mice. The hydrolytic activities against triacylglycerol (TG), diacylglycerol (DG) analog, and CE were increased in transgenic mouse AT. However, cAMP-inducible adipocyte lipolysis was lower in transgenic animals. In the B6CBA genetic background, transgenic mice up to 14 weeks of age showed lower body weight and fat mass. The phenotype was not observed in older animals and in mice fed a high-fat diet (HFD). In the OF1 genetic background, there was no difference in fat mass of mice fed ad libitum. However, transgenic mice became leaner than their wild-type (WT) littermates after a 4 day calorie restriction.

The data show that overexpression of HSL, despite increased lipase activity, does not lead to enhanced lipolysis.

Abbreviations: ALBP, adipocyte lipid binding protein; AT, adipose tissue; BAT, brown adipose tissue; CE, cholesteryl ester; C/EBP, CCAAT/enhancer binding protein ; HFD, high-fat diet; mHSL, murine HSL; MOME, 1(3)-mono-oleoyl-2-O-mono-oleylglycerol; PPAR₂, peroxisome proliferator-activated receptor ₂; SREBP, sterol response element binding protein; Tg, transgenic; WAT, white adipose tissue; WT, wild type

Supplementary key words adipocyte • fat mobilization • transgenesis • skeletal muscle

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