Document Detail


Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis.
MedLine Citation:
PMID:  11717312     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hormone-sensitive lipase (HSL) is expressed predominantly in white and brown adipose tissue where it is believed to play a crucial role in the lipolysis of stored triglycerides (TG), thereby providing the body with energy substrate in the form of free fatty acids (FFA). From in vitro assays, HSL is known to hydrolyze TG, diglycerides (DG), cholesteryl esters, and retinyl esters. In the current study we have generated HSL knock-out mice and demonstrate three lines of evidence that HSL is instrumental in the catabolism of DG in vivo. First, HSL deficiency in mice causes the accumulation of DG in white adipose tissue, brown adipose tissue, skeletal muscle, cardiac muscle, and testis. Second, when tissue extracts were used in an in vitro lipase assay, a reduced FFA release and the accumulation of DG was observed in HSL knock-out mice which did not occur when tissue extracts from control mice were used. Third, in vitro lipolysis experiments with HSL-deficient fat pads demonstrated that the isoproterenol-stimulated release of FFA was decreased and DG accumulated intracellularly resulting in the essential absence of the isoproterenol-stimulated glycerol formation typically observed in control fat pads. Additionally, the absence of HSL in white adipose tissue caused a shift of the fatty acid composition of the TG moiety toward increased long chain fatty acids implying a substrate specificity of the enzyme in vivo. From these in vivo results we conclude that HSL is the rate-limiting enzyme for the cellular catabolism of DG in adipose tissue and muscle.
Authors:
Guenter Haemmerle; Robert Zimmermann; Marianne Hayn; Christian Theussl; Georg Waeg; Elke Wagner; Wolfgang Sattler; Thomas M Magin; Erwin F Wagner; Rudolf Zechner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-11-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-11     Completed Date:  2002-03-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4806-15     Citation Subset:  IM    
Affiliation:
Institute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz A-8010, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism*
Animals
Blotting, Southern
Chromatography, Thin Layer
DNA / metabolism
DNA, Complementary / metabolism
Diglycerides / biosynthesis,  metabolism*
Fatty Acids / metabolism
Genetic Vectors
Isoproterenol / metabolism
Lipid Metabolism
Male
Mass Spectrometry
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Models, Genetic
Muscle, Skeletal / metabolism
Muscles / metabolism*
Myocardium / metabolism
RNA / metabolism
Recombination, Genetic
Sodium Chloride / pharmacology
Sterol Esterase / deficiency*,  genetics*
Testis / metabolism*
Time Factors
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Diglycerides; 0/Fatty Acids; 63231-63-0/RNA; 7647-14-5/Sodium Chloride; 7683-59-2/Isoproterenol; 9007-49-2/DNA; EC 3.1.1.13/Sterol Esterase

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


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