Thiazolidinediones are potent antidiabetic compounds, in both animal and human models, which act by enhancing peripheral sensitivity to insulin. Thiazolidinediones are high-affinity ligands for peroxisome proliferator-activated receptor-γ, a key factor for adipocyte differentiation, and they are efficient promoters of adipocyte differentiation in vitro. Thus, it could be questioned whether a thiazolidinedione therapy aimed at improving insulin sensitivity would promote the recruitment of new adipocytes in vivo. To address this problem, we have studied the in vivo effect of pioglitazone on glucose metabolism and gene expression in the adipose tissue of an animal model of obesity with insulin resistance, the obese Zucker (fa/fa) rat. Pioglitazone markedly improves insulin action in the obese Zucker (fa/fa) rat, but doubles its weight gain after 4 weeks of treatment. The drug induces a large increase of glucose utilization in adipose tissue, where it stimulates the expression of genes involved in lipid metabolism such as the insulin-responsive GLUT, fatty acid synthase, and phospho-enolpyruvate carboxykinase genes, but decreases the expression of the ob gene. These changes are related to both an enhanced adipocyte differentiation, as shown by the large increase in the number of small adipocytes in the retroperitoneal fat pad, and a direct effect of pioglitazone on specific gene expression (phosphoenolpyruvate carboxykinase and ob genes) in mature adipocytes.
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Original Articles|
September 01 1997
Pioglitazone Induces In Vivo Adipocyte Differentiation in the Obese Zucker fa/fa Rat
Sophie Haliakon;
Sophie Haliakon
Institut National de la Santé et de la Recherche Médicale
(INSERM) Unit 465, Paris
LIPHA Research Laboratory
Chilly-Mazarin
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Liliane Doaré;
Liliane Doaré
LIPHA Research Laboratory
Chilly-Mazarin
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Fabienne Foufelle;
Fabienne Foufelle
Institut National de la Santé et de la Recherche Médicale
(INSERM) Unit 465, Paris
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Micheline Kergoat;
Micheline Kergoat
LIPHA Research Laboratory
Chilly-Mazarin
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Michèle Guerre-Millo;
Michèle Guerre-Millo
Institut National de la Santé et de la Recherche Médicale
(INSERM) Unit 465, Paris
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Marie-France Berthault;
Marie-France Berthault
Unité de Recherche Associée (URA) 307
Paris
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Isabelle Dugail;
Isabelle Dugail
Institut National de la Santé et de la Recherche Médicale
(INSERM) Unit 465, Paris
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Pascal Ferré
Pascal Ferré
Institut National de la Santé et de la Recherche Médicale
(INSERM) Unit 465, Paris
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Address correspondence to Pascal Ferré, INSERM Unit 465, Centre Biomédical des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris cedex 06, France. E-mail: [email protected].
Diabetes 1997;46(9):1393–1399
Article history
Received:
December 09 1996
Revision Received:
April 25 1997
Accepted:
April 25 1997
PubMed:
9287037
Citation
Sophie Haliakon, Liliane Doaré, Fabienne Foufelle, Micheline Kergoat, Michèle Guerre-Millo, Marie-France Berthault, Isabelle Dugail, Joëlle Morin, Johan Auwerx, Pascal Ferré; Pioglitazone Induces In Vivo Adipocyte Differentiation in the Obese Zucker fa/fa Rat. Diabetes 1 September 1997; 46 (9): 1393–1399. https://doi.org/10.2337/diab.46.9.1393
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