%0 Journal Article
%T A novel genetically-obese rat model with elevated 11beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue
%A Sakamuri Prasad
%A Anamthathmakula Prashanth
%A Chodavarapu Kumar
%A Sirisha J Reddy
%A Nappan V Giridharan
%A Ayyalasomayajula Vajreswari
%J Lipids in Health and Disease
%D 2010
%I BioMed Central
%R 10.1186/1476-511x-9-132
%X Glucocorticoids are essential for the regulation of metabolism, normal functioning of nervous, cardiovascular, skeletal and immune systems. They are also implicated in the pathogenesis of obesity and metabolic syndrome as evidenced by the fact that, elevated systemic glucocorticoid concentration in Cushing's syndrome results in the development of metabolic syndrome including visceral obesity. The role of plasma glucocorticoids in the development of idiopathic obesity is not clear, as their levels are not altered or sometimes even low in obese patients [1].Tissue sensitivity to glucocorticoids depends on plasma hormone levels, density of glucocorticoid receptors and local metabolism of glucocorticoids by 11¦Â-hydroxysteroid dehydrogenases. 11¦Â-hydroxysteroid dehydrogenase type 1 (11¦Â-HSD1) catalyzes the conversion of inactive glucocorticoids (cortisone in humans and 11-dehydrocorticosterone in rodents) to active glucocorticoids (cortisol in humans and corticosterone in rodents) [2]. It is highly expressed in liver, adipose tissue and brain [2]. Another enzyme, 11¦Â-HSD2 catalyses the reverse reaction and expressed in distal nephron, sweat and salivary glands [3].Recently, it has been reported that 11¦Â-HSD1 plays an important role in the development of obesity and insulin resistance. In obese zuckar rats and in obese human subjects, 11¦Â-HSD1 activity is higher in adipose tissue, where as in liver it is low [4-6]. The role of 11¦Â-HSD1 in obesity and metabolic syndrome is further supported by the transgenic animal model studies. Adipose-specific overexpression of 11¦Â-HSD1 in mice resulted in the development of majority of metabolic syndrome features including visceral obesity and insulin resistance [7], where as 11¦Â-HSD1 knock-out in mice resulted in the development of resistance to diet-induced obesity [8]. Recently, selective inhibitors of 11¦Â-HSD1 are developed to treat obesity and metabolic syndrome.Rodent models of obesity provide valuable information on the molecula
%U http://www.lipidworld.com/content/9/1/132