Document Detail


Adipocyte lipases and defect of lipolysis in human obesity.
MedLine Citation:
PMID:  16249444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity.
Authors:
Dominique Langin; Andrea Dicker; Geneviève Tavernier; Johan Hoffstedt; Aline Mairal; Mikael Rydén; Erik Arner; Audrey Sicard; Christopher M Jenkins; Nathalie Viguerie; Vanessa van Harmelen; Richard W Gross; Cecilia Holm; Peter Arner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes     Volume:  54     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-26     Completed Date:  2006-01-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3190-7     Citation Subset:  AIM; IM    
Affiliation:
Obesity Research Unit, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier (UPS) U586, Louis Bugnard Institute, Toulouse University Hospitals, Toulouse, France. langin@toulouse.inserm.fr
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects,  enzymology*
Adipose Tissue / drug effects,  enzymology*
Adult
Female
Gene Expression Regulation, Enzymologic
Humans
Isoproterenol / pharmacology
Lipase / metabolism*
Lipolysis*
Male
Middle Aged
Obesity / enzymology,  metabolism*
Sterol Esterase / metabolism
Chemical
Reg. No./Substance:
7683-59-2/Isoproterenol; EC 3.1.1.13/Sterol Esterase; EC 3.1.1.3/Lipase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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