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Originally published In Press as doi:10.1074/jbc.M208513200 on December 13, 2002

J. Biol. Chem., Vol. 278, Issue 8, 6510-6515, February 21, 2003
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Hormone-sensitive Lipase Is a Cholesterol Esterase of the Intestinal Mucosa*

Jacques GroberDagger , Stéphanie Lucas§, Maria Sörhede-Winzell||, Isabelle ZaghiniDagger , Aline Mairal§, Juan-Antonio Contreras||, Philippe BesnardDagger , Cecilia Holm||**, and Dominique Langin§Dagger Dagger

From the Dagger  Laboratoire de Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation, FRE2328 CNRS/Université de Bourgogne 1, Dijon 21000, France, the § Unité de Recherches sur les Obésités, INSERM, Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse 31403, France, and the || Department of Cell and Molecular Biology, Section for Molecular Signaling, Lund University, Lund 221 84, Sweden

The identity of the enzymes responsible for lipase and cholesterol esterase activities in the small intestinal mucosa is not known. Because hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters, we sought to determine whether HSL could be involved. HSL mRNA and protein were detected in all segments of the small intestine by Northern and Western blot analyses, respectively. Immunocytochemistry experiments revealed that HSL was expressed in the differentiated enterocytes of the villi and was absent in the undifferentiated cells of the crypt. Diacylglycerol lipase and cholesterol esterase activities were found in the different segments. Analysis of gut from HSL-null mice showed that diacylglycerol lipase activity was unchanged in the duodenum and reduced in jejunum. Neutral cholesterol esterase activity was totally abolished in duodenum, jejunum, and ileum of HSL-null mice. Analysis of HSL mRNA structure showed two types of transcripts expressed in equal amounts with alternative 5'-ends transcribed from two exons. This work demonstrates that HSL is expressed in the mucosa of the small intestine. The results also reveal that the enzyme participates in acylglycerol hydrolysis in jejunal enterocytes and cholesteryl ester hydrolysis throughout the small intestine.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by doctoral grants from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche, and the Fondation pour la Recherche Médicale.

** Supported by the Swedish Research Council Project 112 84 and the A. Påhlsson Foundation.

Dagger Dagger To whom correspondence should be addressed: INSERM U317, Bâtiment L3, CHU Rangueil, 31403 Toulouse Cedex 4, France. Tel.: 33-562-172-950; Fax: 33-561-331-721; E-mail: Dominique.Langin@toulouse.inserm.fr.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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