Document Detail


Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids.
MedLine Citation:
PMID:  19088251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adiponectin, made exclusively by adipocytes, is a 30-kDa secretory protein assembled posttranslationally into low-molecular weight, middle-molecular weight, and high-molecular weight homo-oligomers. PPARgamma ligand thiozolidinediones, which are widely used in the treatment of type II diabetes, increase adiponectin levels. PPARgamma also has several putative ligands that include fatty acid derivatives. Overnight treatment of rat adipocytes with pioglitazone, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) triggered a twofold increase in the synthesis and secretion of HMW adiponectin, and this increase was blocked by the addition of PPARgamma inhibitor GW-9662. Inhibition of glycosylation using 2,2'-dipyridyl decreased the synthesis of high-molecular weight adiponectin by pioglitazone, EPA, and DHA, but there was increased secretion of trimeric adiponectin resulting from increased translation. Although pioglitazone, DHA, and EPA increased adiponectin synthesis by more than 60%, there was no increase in total protein synthesis and no corresponding change in adiponectin mRNA expression, indicating the upregulation of translation. We examined the possibility of transacting factors in the cytoplasmic extracts from adipocytes treated with pioglitazone or DHA. In vitro translation of adiponectin mRNA was inhibited by S-100 fraction of control adipocytes and increased by S-100 extracts from adipocytes treated with pioglitazone or DHA. Consistent with this observation, both pioglitazone and DHA treatments increased the association of adiponectin mRNA with the heavier polysome fractions. Together, these data suggest that pioglitazone and the fish oils DHA or EPA are PPARgamma agonists in adipocytes with regard to adiponectin expression, and the predominant mode of adiponectin stimulation is via an increase in translation.
Authors:
Anannya Banga; Resat Unal; Preeti Tripathi; Irina Pokrovskaya; Randall J Owens; Philip A Kern; Gouri Ranganathan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-12-16
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  296     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-23     Completed Date:  2009-04-20     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E480-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / cytology,  drug effects,  physiology
Adiponectin / genetics*,  metabolism,  secretion
Animals
Cells, Cultured
Docosahexaenoic Acids / pharmacology
Eicosapentaenoic Acid / pharmacology
Fatty Acids, Omega-3 / pharmacology*
Gene Expression Regulation / drug effects,  physiology
Hypoglycemic Agents / pharmacology*
Male
PPAR gamma / agonists*,  metabolism
Protein Biosynthesis / drug effects*,  physiology
Rats
Rats, Sprague-Dawley
Thiazolidinediones / pharmacology*
Grant Support
ID/Acronym/Agency:
DK-080327/DK/NIDDK NIH HHS; DK-39176/DK/NIDDK NIH HHS; R01 DK080327/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Fatty Acids, Omega-3; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 25167-62-8/Docosahexaenoic Acids; AAN7QOV9EA/Eicosapentaenoic Acid; X4OV71U42S/pioglitazone
Comments/Corrections

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


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