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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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mRNA and protein expression of markers of GC action and gluconeogenesis in the liver of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A) 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 GAPDH expression. Mean ± SEM of n = 7–8 rats per group. *P<0.05 compared to vehicle-infused control rats (Student's t test). B and C) Representative Western blots of 11β-HSD1 and PEPCK (n = 4–5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software.
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pone-0034002-g005: mRNA and protein expression of markers of GC action and gluconeogenesis in the liver of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A) 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 GAPDH expression. Mean ± SEM of n = 7–8 rats per group. *P<0.05 compared to vehicle-infused control rats (Student's t test). B and C) Representative Western blots of 11β-HSD1 and PEPCK (n = 4–5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software.

Mentions: In contrast to what was observed in Wistar rats, a significant decrease in 11β-HSD1 mRNA expression was observed in the liver of dexamethasone-treated SD rats (P = 0.007), with a similar expression for H6PDH (Fig. 5A), both parameters being highly correlated (r2 = 0.692, P = 0.001). 11β-HSD1 protein expression also tended to decrease (Fig. 5B). In addition, PEPCK mRNA expression was reduced in dexamethasone-treated rats (P = 0.016) (Fig. 5A) and there was a significant correlation between PEPCK and 11β-HSD1 expression in this tissue (r2 = 0.353, P = 0.032). PEPCK protein levels were, however, unaltered by central dexamethasone infusion (Fig. 5C).


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)

mRNA and protein expression of markers of GC action and gluconeogenesis in the liver of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A) 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 GAPDH expression. Mean ± SEM of n = 7–8 rats per group. *P<0.05 compared to vehicle-infused control rats (Student's t test). B and C) Representative Western blots of 11β-HSD1 and PEPCK (n = 4–5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316512&req=5

pone-0034002-g005: mRNA and protein expression of markers of GC action and gluconeogenesis in the liver of SD rats.Effects of central (icv) dexamethasone infusion for 2 days. A) 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 GAPDH expression. Mean ± SEM of n = 7–8 rats per group. *P<0.05 compared to vehicle-infused control rats (Student's t test). B and C) Representative Western blots of 11β-HSD1 and PEPCK (n = 4–5 per group). Quantification was performed using the ChemiDoc™ XRS and the Quantity One™ software.
Mentions: In contrast to what was observed in Wistar rats, a significant decrease in 11β-HSD1 mRNA expression was observed in the liver of dexamethasone-treated SD rats (P = 0.007), with a similar expression for H6PDH (Fig. 5A), both parameters being highly correlated (r2 = 0.692, P = 0.001). 11β-HSD1 protein expression also tended to decrease (Fig. 5B). In addition, PEPCK mRNA expression was reduced in dexamethasone-treated rats (P = 0.016) (Fig. 5A) and there was a significant correlation between PEPCK and 11β-HSD1 expression in this tissue (r2 = 0.353, P = 0.032). PEPCK protein levels were, however, unaltered by central dexamethasone infusion (Fig. 5C).

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