title: Central glucocorticoid administration promotes weight gain and increased 11β-hydroxysteroid dehydrogenase type 1 expression in white adipose tissue.
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.
authors.affiliation: Laboratory of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. christelle.veyrat-durebex@unige.ch
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deblon
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caillon
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.forename: Jordi
authors.initials: J
authors.lastname: Altirriba
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage*; D057967:Infusions, Intraventricular; D055104:Infusions, Subcutaneous; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D005938:Glucocorticoids; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1