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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
Hormone-sensitive Lipase Is a Cholesterol Esterase of the
Intestinal Mucosa*
Jacques
Grober ,
Stéphanie
Lucas§¶,
Maria
Sörhede-Winzell ,
Isabelle
Zaghini ,
Aline
Mairal§,
Juan-Antonio
Contreras ,
Philippe
Besnard ,
Cecilia
Holm **, and
Dominique
Langin§
From the 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.

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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