Document Detail


Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL.
MedLine Citation:
PMID:  10950827     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P < 0.05), triglyceride (TG; P < 0.001), and insulin (P < 0.05) concentrations. In addition, isoproterenol-induced lipolytic rate and HSL activity were significantly lower (P < 0.001) in adipocytes isolated from masoprocol compared with vehicle-treated rats and was associated with a decrease in HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.
Authors:
M S Gowri; R K Azhar; F B Kraemer; G M Reaven; S Azhar
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  279     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-09-19     Completed Date:  2000-09-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E593-600     Citation Subset:  IM    
Affiliation:
Stanford University School of Medicine, CA 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / cytology,  drug effects,  enzymology
Animals
Blood Glucose / metabolism
DNA Probes
Diet
Fatty Acids, Nonesterified / blood
Indicators and Reagents
Kinetics
Lipolysis / drug effects*
Lipoxygenase Inhibitors / pharmacology*
Male
Nordihydroguaiaretic Acid / pharmacology*
Phosphorylation
Precipitin Tests
RNA Probes
RNA, Messenger / biosynthesis
Rats
Rats, Sprague-Dawley
Sterol Esterase / drug effects,  metabolism*
Triglycerides / blood
Grant Support
ID/Acronym/Agency:
DK-46942/DK/NIDDK NIH HHS; DK-49705/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/DNA Probes; 0/Fatty Acids, Nonesterified; 0/Indicators and Reagents; 0/Lipoxygenase Inhibitors; 0/RNA Probes; 0/RNA, Messenger; 0/Triglycerides; 500-38-9/Nordihydroguaiaretic Acid; EC 3.1.1.13/Sterol Esterase

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


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