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Papers In Press, published online ahead of print October 16, 2002
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Submitted on June 28, 2002
INSERM U317, Institut Louis Bugnard, Toulouse 31403
Corresponding Author: langin{at}toulouse.inserm.fr
Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters. The enzyme is highly expressed in adipose tissues 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. Human HSL mRNA was expressed at 3-fold higher levels than murine HSL mRNA in white adipocytes. Transgene expression was also observed in brown adipose tissue and skeletal muscle. The human protein was detected in adipose tissues of transgenic mice. The hydrolytic activities against TG, DG analogue and cholesteryl ester were increased in transgenic mouse adipose tissues. However, cAMP-inducible adipocyte lipolysis was lower in transgenic animals. On 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. On 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 littermates after a 4 day calorie restriction. The data show that overexpression of HSL, despite increased lipase activity, does not lead to enhanced lipolysis.
Revised on October 8, 2002
Accepted on October 11, 2002
Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis
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