Central Glucocorticoid Administration Promotes Weight Gain and Increased 11b-Hydroxysteroid Dehydrogenase Type 1 Expression in White Adipose Tissue

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 11b-hydroxysteroid dehydrogenase type 1 (11b-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 11b-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 11b-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 11b-HSD1 and resistin expression in adipose tissue. A decrease 11b-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. Citation: Veyrat-Durebex C, Deblon N, Caillon A, Andrew R, Altirriba J, et al. (2012) Central Glucocorticoid Administration Promotes Weight Gain and Increased 11b-Hydroxysteroid Dehydrogenase Type 1 Expression in White Adipose Tissue. PLoS ONE 7(3): e34002. doi:10.1371/journal.pone.0034002 Editor: Silvana Gaetani, Sapienza University of Rome, Italy Received July 12, 2011; Accepted February 24, 2012; Published March 30, 2012 Copyright: 2012 Veyrat-Durebex et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the Swiss National Science Foundation grants Nu3100AO-105889 to FR-J, and Nu310000-112279 to AO, as well as by the EUFP6 grant LSHM-CT-2003-503041 to FR-J. The funders had no role in study design, data collection and analyses, decision to publish or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]