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

被引:25
|
作者
Veyrat-Durebex, Christelle [1 ]
Deblon, Nicolas [1 ]
Caillon, Aurelie [1 ]
Andrew, Ruth [2 ]
Altirriba, Jordi [1 ]
Odermatt, Alex [3 ]
Rohner-Jeanrenaud, Francoise [1 ]
机构
[1] Univ Geneva, Lab Metab, Dept Internal Med, Fac Med, Geneva, Switzerland
[2] Queens Med Res Inst, Mass Spectrometry Core Lab, Edinburgh, Midlothian, Scotland
[3] Univ Basel, Dept Pharmaceut Sci, Div Mol & Syst Toxicol, Basel, Switzerland
来源
PLOS ONE | 2012年 / 7卷 / 03期
基金
瑞士国家科学基金会;
关键词
DIET-INDUCED OBESITY; CCAAT/ENHANCER-BINDING PROTEINS; INSULIN-RESISTANCE; METABOLIC SYNDROME; ZUCKER RATS; HEXOSE-6-PHOSPHATE DEHYDROGENASE; VISCERAL OBESITY; IMPAIRS INSULIN; STROMAL CELLS; WISTAR RATS;
D O I
10.1371/journal.pone.0034002
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-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 11 beta-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 11 beta-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 11 beta-HSD1 and resistin expression in adipose tissue. A decrease 11 beta-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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页数:12
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