J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M500081-JLR200 on June 16, 2005

Papers In Press, published online ahead of print September 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500081-JLR200
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
M500081-JLR200v1
46/9/1860    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fortier, M.
Right arrow Articles by Mitchell, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fortier, M.
Right arrow Articles by Mitchell, G. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 46, 1860-1867, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice

Mélanie Fortier*, Krishnakant Soni*, Nancy Laurin1,*, Shu Pei Wang*, Pascale Mauriège{dagger}, Frank R. Jirik§ and Grant A. Mitchell2,*

* Division of Medical Genetics, Research Centre, Sainte-Justine Hospital, Montréal, Québec, Canada
{dagger} Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Ste-Foy, Quebec, Canada
§ Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

The online version of this article (available at http://www.jlr.org) contains an additional table.

Published, JLR Papers in Press, June 16, 2005. DOI 10.1194/jlr.M500081-JLR200

1 Present address of N. Laurin: Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada M5G 2C4.

2 To whom correspondence should be addressed. e-mail: grant.mitchell{at}recherche-ste-justine.qc.ca

In white adipose tissue (WAT), hormone-sensitive lipase (HSL) can mediate lipolysis, a central pathway in obesity and diabetes. Gene-targeted HSL-deficient (HSL–/–) mice with no detectable HSL peptide or activity (measured as cholesteryl esterase) have WAT abnormalities, including low mass, marked heterogeneity of cell diameter, increased diacylglycerol content, and low ß-adrenergic stimulation of adipocyte lipolysis. Three transgenic mouse strains preferentially expressing human HSL in WAT were bred to a HSL–/– background. One, HSL–/–N, expresses normal human HSL (41.3 ± 9.1% of normal activity); two express a serine-to-alanine mutant (S554A) initially hypothesized to be constitutively active: HSL–/–ML, 50.3 ± 12.3% of normal, and HSL–/–MH, 69.8 ± 15.8% of normal. In WAT, HSL–/–N mice resembled HSL+/+ controls in WAT mass, histology, diacylglyceride content, and lipolytic response to ß-adrenergic agents. In contrast, HSL–/– ML and HSL–/–MH mice resembled nontransgenic HSL–/– mice, except that diacylglycerol content and perirenal and inguinal WAT masses approached normal in HSL–/–MH mice.

Therefore, 1) WAT expression of normal human HSL markedly improves HSL–/– WAT biochemically, physiologically, and morphologically; 2) similar levels of S554A HSL have a low physiological effect despite being active in vitro; and 3) diacylglycerol accumulation is not essential for the development of the characteristic WAT pathology of HSL–/– mice.

Abbreviations: aP2, adipocyte fatty acid binding protein; DG, diglyceride; HSL, hormone-sensitive lipase; HSL–/–, hormone-sensitive lipase-deficient; TG, triglyceride; WAT, white adipose tissue

Supplementary key words hormone-sensitive lipase • adipocyte • mouse • mutation • fat metabolism


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.