Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents

Harleen Singh Ahuja, Sha Liu, Diane L. Crombie, Marcus Boehm, Mark D. Leibowitz, Richard A. Heyman, Christophe Depre, L. Nagy, Peter Tontonoz, Peter J A Davies

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Abstract

Both retinoid X receptor (RXR)-selective agonists (rexinoids) and thiazolidinediones (TZDs), PPAR (peroxisome proliferator-activated receptor)-γ-specific ligands, produce insulin sensitization in diabetic rodents. In vitro studies have demonstrated that TZDs mediate their effects via the RXR/PPAR-γ complex. To determine whether rexinoids lower hyperglycemia by activating the RXR/PPAR-γ, heterodimer in vivo, we compared the effects of a rexinoid (LG100268) and a TZD (rosiglitazone) on gene expression in white adipose tissue, skeletal muscle, and liver of Zucker diabetic fatty rats (ZDFs). In adipose tissue, rosiglitazone decreased tumor necrosis factor-α (TNF-α) mRNA and induced glucose transporter 4 (GLUT4), muscle carnitine palmitoyl-transferase (MCPT), stearoyl CoA desaturase (SCD1), and fatty acid translocase (CD36). In contrast, LG100268 increased TNF-α and had no effect or suppressed the expression of GLUT4, MCPT, SCD1, and CD36. In liver, the rexinoid increased MCPT, SCD1, and CD36 mRNAs, whereas rosiglitazone induced only a small increase in CD36. In skeletal muscle, rosiglitazone and LG100268 have similar effects; both creased SCD1 and CD36 mRNAs. The differences in the pattern of genes induced by the rexinoids and the TZDs in diabetic animals found in these studies suggests that these compounds may have independent and tissue-specific effects on metabolic control in vivo.

Original languageEnglish
Pages (from-to)765-773
Number of pages9
JournalMolecular Pharmacology
Volume59
Issue number4
Publication statusPublished - 2001

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rosiglitazone
Thiazolidinediones
Retinoid X Receptors
Peroxisome Proliferator-Activated Receptors
Carnitine
Rodentia
Transferases
Gene Expression
Facilitative Glucose Transport Proteins
Muscles
Messenger RNA
Skeletal Muscle
Tumor Necrosis Factor-alpha
Stearoyl-CoA Desaturase
White Adipose Tissue
Liver
Hyperglycemia
Adipose Tissue
Fatty Acids
Insulin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ahuja, H. S., Liu, S., Crombie, D. L., Boehm, M., Leibowitz, M. D., Heyman, R. A., ... Davies, P. J. A. (2001). Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Molecular Pharmacology, 59(4), 765-773.

Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. / Ahuja, Harleen Singh; Liu, Sha; Crombie, Diane L.; Boehm, Marcus; Leibowitz, Mark D.; Heyman, Richard A.; Depre, Christophe; Nagy, L.; Tontonoz, Peter; Davies, Peter J A.

In: Molecular Pharmacology, Vol. 59, No. 4, 2001, p. 765-773.

Research output: Contribution to journalArticle

Ahuja, HS, Liu, S, Crombie, DL, Boehm, M, Leibowitz, MD, Heyman, RA, Depre, C, Nagy, L, Tontonoz, P & Davies, PJA 2001, 'Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents', Molecular Pharmacology, vol. 59, no. 4, pp. 765-773.
Ahuja HS, Liu S, Crombie DL, Boehm M, Leibowitz MD, Heyman RA et al. Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Molecular Pharmacology. 2001;59(4):765-773.
Ahuja, Harleen Singh ; Liu, Sha ; Crombie, Diane L. ; Boehm, Marcus ; Leibowitz, Mark D. ; Heyman, Richard A. ; Depre, Christophe ; Nagy, L. ; Tontonoz, Peter ; Davies, Peter J A. / Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. In: Molecular Pharmacology. 2001 ; Vol. 59, No. 4. pp. 765-773.
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