Document Detail

Involvement of adipose tissues in the early hypolipidemic action of PPARgamma agonism in the rat.
MedLine Citation:
PMID:  17170230     Owner:  NLM     Status:  MEDLINE    
Agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma) are insulin sensitizers that potently improve lipemia in rodents. This study aimed to determine the contribution of lipid secretion vs. clearance and the involvement of white adipose tissue (WAT) and brown adipose tissue (BAT) in the rapid hypolipidemic action of PPARgamma agonism. Male rats were treated with rosiglitazone (RSG; 15 mg x kg(-1) x day(-1)) for 1 to 4 days, and determinants of lipid metabolism were assessed postprandially. Serum triglycerides (TG) were lowered (-54%) after 3 days of RSG treatment, due to accelerated clearance from blood without contribution of changes in secretion rates. Both BAT and WAT were the major sites of RSG action on TG clearance, the increase in TG-derived fatty acid (FA) uptake reaching threefold in BAT and 60-90% in WAT depots. Accelerated TG clearance was associated with increased lipoprotein lipase (LPL) activity mostly in BAT. Serum nonesterified FA were lowered (-20%) by a single dose of RSG, an effect associated with increased expression levels of FA binding/transport (fatty acid binding protein-4), esterification (diacylglycerol acyltransferase-1), and recycling glycerol kinase and phosphoenolpyruvate carboxykinase enzymes in BAT and WAT, suggesting FA trapping. After 4 days of RSG treatment, nonesterified fatty acid (NEFA) uptake was also stimulated in both BAT (2.5-fold) and WAT (40%). These findings demonstrate the causal involvement of increased efficiency of LPL-mediated TG clearance and reveal the important contribution of TG-derived and albumin-bound FA uptake by BAT in the rapid hypolipidemic action of PPARgamma agonism in the rat.
Mathieu Laplante; William T Festuccia; Geneviève Soucy; Yves Gélinas; Josée Lalonde; Yves Deshaies
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-14
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  292     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-04     Completed Date:  2007-05-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1408-17     Citation Subset:  IM    
Laval Hospital Research Center, Laval Hospital-d'Youville Y3110, 2725 Chemin Sainte-Foy, Quebec, QC, Canada, G1V 4G5.
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MeSH Terms
Adipose Tissue, Brown / drug effects*,  enzymology,  metabolism
Adipose Tissue, White / drug effects*,  enzymology,  metabolism
Esterification / drug effects
Fatty Acid-Binding Proteins / blood,  metabolism
Fatty Acids, Nonesterified / blood,  genetics,  metabolism
Glycerol Kinase / metabolism
Hypoglycemic Agents / pharmacology*
Lipoprotein Lipase / genetics,  metabolism
PPAR gamma / agonists*
Phosphoenolpyruvate Carboxykinase (GTP) / metabolism
Rats, Sprague-Dawley
Thiazolidinediones / pharmacology*
Time Factors
Triglycerides / blood
Reg. No./Substance:
0/Fatty Acid-Binding Proteins; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 0/Triglycerides; 122320-73-4/rosiglitazone; EC Kinase; EC Lipase; EC Carboxykinase (GTP)

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

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