HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kershaw, E. E. Articles by Flier, J. S. Search for Related Content PubMed PubMed Citation Articles by Kershaw, E. E. Articles by Flier, J. S. Social Bookmarking                What's this?

Adipocyte-Specific Glucocorticoid Inactivation Protects Against Diet-Induced Obesity

¹ Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
² Endocrinology Unit, Molecular Medicine Center, University of Edinburgh, Western General Hospital, Edinburgh, U.K

Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11ß-hydroxysteroid dehydrogenases (11ßHSDs). 11ßHSD1 activates GCs, while 11ßHSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11ßHSD1 produces visceral obesity and the metabolic syndrome in mice. To determine whether adipocyte-specific inactivation of GCs protects against this phenotype, we created a transgenic model in which human 11ßHSD2 is expressed under the control of the murine adipocyte fatty acid binding protein (aP2) promoter (aP2-h11ßHSD2). Transgenic mice have increased 11ßHSD2 expression and activity exclusively in adipose tissue, with the highest levels in subcutaneous adipose tissue, while systemic indexes of GC exposure are unchanged. Transgenic mice resist weight gain on high-fat diet due to reduced fat mass accumulation. This improved energy balance is associated with decreased food intake, increased energy expenditure, and improved glucose tolerance and insulin sensitivity. Adipose tissue gene expression in transgenic mice is characterized by decreased expression of leptin and resistin and increased expression of adiponectin, peroxisome proliferator–activated receptor , and uncoupling protein 2. These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Boullu-Ciocca, V. Achard, V. Tassistro, A. Dutour, and M. Grino Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet-Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood Diabetes, March 1, 2008; 57(3): 669 - 677. [Abstract] [Full Text] [PDF]

				K. L. K. Tamashiro, M. M. N. Nguyen, M. M. Ostrander, S. R. Gardner, L. Y. Ma, S. C. Woods, and R. R. Sakai Social stress and recovery: implications for body weight and body composition Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1864 - R1874. [Abstract] [Full Text] [PDF]

				M. Caprio, B. Feve, A. Claes, S. Viengchareun, M. Lombes, and M.-C. Zennaro Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis FASEB J, July 1, 2007; 21(9): 2185 - 2194. [Abstract] [Full Text] [PDF]

				J. Kim, K. A. Temple, S. A. Jones, K. N. Meredith, J. L. Basko, and M. J. Brady Differential Modulation of 3T3-L1 Adipogenesis Mediated by 11beta-Hydroxysteroid Dehydrogenase-1 Levels J. Biol. Chem., April 13, 2007; 282(15): 11038 - 11046. [Abstract] [Full Text] [PDF]

				S. Nakano, Y. Inada, H. Masuzaki, T. Tanaka, S. Yasue, T. Ishii, N. Arai, K. Ebihara, K. Hosoda, K. Maruyama, et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1213 - E1222. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, M. Sherlock, B. Hughes, S. V. Hughes, F. Kilvington, W. Bartlett, R. Courtney, P. Rejto, W. Carley, and P. M. Stewart Inhibition of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity in Vivo Limits Glucocorticoid Exposure to Human Adipose Tissue and Decreases Lipolysis J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 857 - 864. [Abstract] [Full Text] [PDF]

				D. Qi and B. Rodrigues Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E654 - E667. [Abstract] [Full Text] [PDF]

				A. McMaster and D. W. Ray Modelling the glucocorticoid receptor and producing therapeutic agents with anti-inflammatory effects but reduced side-effects Exp Physiol, March 1, 2007; 92(2): 299 - 309. [Abstract] [Full Text] [PDF]

				V. S. Densmore, N. M. Morton, J. J. Mullins, and J. R. Seckl 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Induction in the Arcuate Nucleus by High-Fat Feeding: A Novel Constraint to Hyperphagia? Endocrinology, September 1, 2006; 147(9): 4486 - 4495. [Abstract] [Full Text] [PDF]

				S. K. Paulsen, S. B. Pedersen, J. O. L. Jorgensen, S. Fisker, J. S. Christiansen, A. Flyvbjerg, and B. Richelsen Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1093 - 1098. [Abstract] [Full Text] [PDF]