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Central glucocorticoid administration promotes weight gain and increased 11β-hydroxysteroid dehydrogenase type 1 expression in white adipose tissue.

Veyrat-Durebex C, Deblon N, Caillon A, Andrew R, Altirriba J, Odermatt A, Rohner-Jeanrenaud F - PLoS ONE (2012)

Bottom Line: Central GC administration induced a significant increase in body weight gain and in 11β-HSD1 and resistin expression in adipose tissue.A decrease 11β-HSD1 expression was noticed in the liver of SD rats, as a partial compensatory mechanism.Such effects of GCs are centrally elicited.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. christelle.veyrat-durebex@unige.ch

ABSTRACT
Glucocorticoids (GCs) are involved in multiple metabolic processes, including the regulation of insulin sensitivity and adipogenesis. Their action partly depends on their intracellular activation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We previously demonstrated that central GC administration promotes hyperphagia, body weight gain, hyperinsulinemia and marked insulin resistance at the level of skeletal muscles. Similar dysfunctions have been reported to occur upon specific overexpression of 11β-HSD1 in adipose tissue. The aim of the present study was therefore to determine whether the effects of central GC infusion may enhance local GC activation in white adipose tissue. Male Wistar and Sprague Dawley (SD) rats were intracerebroventricularly infused with GCs for 2 to 3 days. Body weight, food intake and metabolic parameters were measured, and expression of enzymes regulating 11β-HSD1, as well as that of genes regulated by GCs, were quantified. Central GC administration induced a significant increase in body weight gain and in 11β-HSD1 and resistin expression in adipose tissue. A decrease 11β-HSD1 expression was noticed in the liver of SD rats, as a partial compensatory mechanism. Such effects of GCs are centrally elicited. This model of icv dexamethasone infusion thus appears to be a valuable acute model, that helps delineating the initial metabolic defects occurring in obesity. An impaired downregulation of intracellular GC activation in adipose tissue may be important for the development of insulin resistance.

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C/EBPα, C/EBPβ mRNA and protein expression in iWAT (A) and in the liver (C) of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A and C) Results are expressed as percent of relative mRNA expression compared to that obtained in control rats (100%). The analysis was performed in duplicate and the results were normalized with RPS29, β-actin and GAPDH expression. Mean ± SEM of n = 7–8 rats per group. B) Representative Western blots of C/EBPα, C/EBPβ and phosphorylated C/EBPβ-ser105 (n = 5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software. *P<0.05 compared to vehicle-infused control rats (Student's t test).
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pone-0034002-g006: C/EBPα, C/EBPβ mRNA and protein expression in iWAT (A) and in the liver (C) of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A and C) Results are expressed as percent of relative mRNA expression compared to that obtained in control rats (100%). The analysis was performed in duplicate and the results were normalized with RPS29, β-actin and GAPDH expression. Mean ± SEM of n = 7–8 rats per group. B) Representative Western blots of C/EBPα, C/EBPβ and phosphorylated C/EBPβ-ser105 (n = 5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software. *P<0.05 compared to vehicle-infused control rats (Student's t test).

Mentions: Recent evidence suggests that the expression ratio of the transcription factors CCAAT enhancer binding protein (C/EBP)α to C/EBPβ might be important for the control of 11β-HSD1 expression [39], [40], [41], [42]. The expression of these two transcription factors was therefore characterized in iWAT and the liver of control and dexamethasone-treated SD rats. First, and as depicted in Fig. 6A, a two-fold increase in C/EBPα mRNA expression was observed in iWAT, in response to central dexamethasone infusion (P = 0.043), while C/EBPβ mRNA expression was unaltered by the treatment. This C/EBPα mRNA increase was highly correlated with the expression of resistin (r2 = 0.905, P = 0.001). When calculating the gene expression ratio of C/EBPα to C/EBPβ, an almost three-fold, although not significant increase was obtained in dexamethasone-treated animals (Fig. 6A). With regard to protein expression measured by Western blot analysis, a though 1.6 fold increase in C/EBPα was observed in the dexamethasone-treated group (Fig. 6B). In this group, both C/EBPβ and P-C/EBPβ expressions similarly increased by 1.86 folds. The resulting ratio between C/EBPα and C/EBPβ was unaltered by dexamethasone infusion at the protein level.


Central glucocorticoid administration promotes weight gain and increased 11β-hydroxysteroid dehydrogenase type 1 expression in white adipose tissue.

Veyrat-Durebex C, Deblon N, Caillon A, Andrew R, Altirriba J, Odermatt A, Rohner-Jeanrenaud F - PLoS ONE (2012)

C/EBPα, C/EBPβ mRNA and protein expression in iWAT (A) and in the liver (C) of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A and C) Results are expressed as percent of relative mRNA expression compared to that obtained in control rats (100%). The analysis was performed in duplicate and the results were normalized with RPS29, β-actin and GAPDH expression. Mean ± SEM of n = 7–8 rats per group. B) Representative Western blots of C/EBPα, C/EBPβ and phosphorylated C/EBPβ-ser105 (n = 5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software. *P<0.05 compared to vehicle-infused control rats (Student's t test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3316512&req=5

pone-0034002-g006: C/EBPα, C/EBPβ mRNA and protein expression in iWAT (A) and in the liver (C) of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A and C) Results are expressed as percent of relative mRNA expression compared to that obtained in control rats (100%). The analysis was performed in duplicate and the results were normalized with RPS29, β-actin and GAPDH expression. Mean ± SEM of n = 7–8 rats per group. B) Representative Western blots of C/EBPα, C/EBPβ and phosphorylated C/EBPβ-ser105 (n = 5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software. *P<0.05 compared to vehicle-infused control rats (Student's t test).
Mentions: Recent evidence suggests that the expression ratio of the transcription factors CCAAT enhancer binding protein (C/EBP)α to C/EBPβ might be important for the control of 11β-HSD1 expression [39], [40], [41], [42]. The expression of these two transcription factors was therefore characterized in iWAT and the liver of control and dexamethasone-treated SD rats. First, and as depicted in Fig. 6A, a two-fold increase in C/EBPα mRNA expression was observed in iWAT, in response to central dexamethasone infusion (P = 0.043), while C/EBPβ mRNA expression was unaltered by the treatment. This C/EBPα mRNA increase was highly correlated with the expression of resistin (r2 = 0.905, P = 0.001). When calculating the gene expression ratio of C/EBPα to C/EBPβ, an almost three-fold, although not significant increase was obtained in dexamethasone-treated animals (Fig. 6A). With regard to protein expression measured by Western blot analysis, a though 1.6 fold increase in C/EBPα was observed in the dexamethasone-treated group (Fig. 6B). In this group, both C/EBPβ and P-C/EBPβ expressions similarly increased by 1.86 folds. The resulting ratio between C/EBPα and C/EBPβ was unaltered by dexamethasone infusion at the protein level.

Bottom Line: Central GC administration induced a significant increase in body weight gain and in 11β-HSD1 and resistin expression in adipose tissue.A decrease 11β-HSD1 expression was noticed in the liver of SD rats, as a partial compensatory mechanism.Such effects of GCs are centrally elicited.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. christelle.veyrat-durebex@unige.ch

ABSTRACT
Glucocorticoids (GCs) are involved in multiple metabolic processes, including the regulation of insulin sensitivity and adipogenesis. Their action partly depends on their intracellular activation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We previously demonstrated that central GC administration promotes hyperphagia, body weight gain, hyperinsulinemia and marked insulin resistance at the level of skeletal muscles. Similar dysfunctions have been reported to occur upon specific overexpression of 11β-HSD1 in adipose tissue. The aim of the present study was therefore to determine whether the effects of central GC infusion may enhance local GC activation in white adipose tissue. Male Wistar and Sprague Dawley (SD) rats were intracerebroventricularly infused with GCs for 2 to 3 days. Body weight, food intake and metabolic parameters were measured, and expression of enzymes regulating 11β-HSD1, as well as that of genes regulated by GCs, were quantified. Central GC administration induced a significant increase in body weight gain and in 11β-HSD1 and resistin expression in adipose tissue. A decrease 11β-HSD1 expression was noticed in the liver of SD rats, as a partial compensatory mechanism. Such effects of GCs are centrally elicited. This model of icv dexamethasone infusion thus appears to be a valuable acute model, that helps delineating the initial metabolic defects occurring in obesity. An impaired downregulation of intracellular GC activation in adipose tissue may be important for the development of insulin resistance.

Show MeSH
Related in: MedlinePlus