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Endocrinology Vol. 139, No. 1 428-431
Copyright © 1998 by The Endocrine Society

ARTICLES

Thiazolidinediones Stimulate Uncoupling Protein-2 Expression in Cell Lines Representing White and Brown Adipose Tissues and Skeletal Muscle

Anne Camirand, Véronique Marie, Rogério Rabelo and J. Enrique Silva

Division of Endocrinology and Metabolism, Lady Davis Institute at Jewish General Hospital, McGill University, Montréal, Québec H3T 1E2, Canada

Address all correspondence and requests for reprints to: J. Enrique Silva, M.D., Jewish General Hospital, Division of Endocrinology, Room E-163, 3755 Cote-St.-Catherine Road, Montréal, Québec H3T 1E2, Canada.


   Abstract
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 Abstract
 
Thiazolidinediones (TZD) are PPARy ligands that sensitize tissues to insulin. A cDNA encoding a mitochondrial protein likely to act as uncoupler (uncoupling protein 2, UCP2) has been recently cloned. Since TZD have been reported to increase energy expenditure in animals, we have examined the effects of these drugs on the expression of UCP2 mRNA in cell lines representing white (3T3-L1 and 3T3-F442A) and brown (HIB-1B) adipose tissues and skeletal muscle (L6). Northern blots probed with a mouse UCP2 full-length cDNA showed a mRNA of 1.6 kb both in tissues and the aforementioned cells lines. Within 4 h of exposing these cells to 30 µM darglitazone, there was an increase in UCP2 mRNA which reached a plateau of 5–10 times the basal in about 8 h. In all cells TZDs (darglitazone, troglitazone) were more active than the predominantly PPAR{alpha} ligands WY-14,613 and clofibrate, or the non-selective ligand linoleic acid. These results indicate that TZDs can stimulate the expression of UCP2 gene probably via PPARy and hence have the potential to increase energy expenditure in adult humans, in whom UCP2 is expressed ubiquitously.

Received October 9, 1997.




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