Adipocyte-Specific Glucocorticoid Inactivation Protects Against Diet-Induced Obesity
| Autor: | Nicholas M. Morton, Jonathan R. Seckl, Lynne Ramage, Erin E. Kershaw, Harveen Dhillon, Jeffrey S. Flier |
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| Rok vydání: | 2005 |
| Předmět: |
Aging
medicine.medical_specialty Endocrinology Diabetes and Metabolism Transgene Gene Expression Adipose tissue Mice Transgenic Biology Fatty Acid-Binding Proteins Weight Gain Article Energy homeostasis Mice chemistry.chemical_compound Insulin resistance 11-beta-Hydroxysteroid Dehydrogenase Type 2 Internal medicine Adipocyte Adipocytes Internal Medicine medicine Animals Obesity Promoter Regions Genetic Glucocorticoids Metabolic Syndrome Adiponectin Leptin medicine.disease Dietary Fats Endocrinology Adipose Tissue chemistry Resistin Insulin Resistance Carrier Proteins hormones hormone substitutes and hormone antagonists |
| Zdroj: | Kershaw, E E, Morton, N M, Dhillon, H, Ramage, L, Seckl, J R & Flier, J S 2005, ' Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity ', Diabetes, vol. 54, no. 4, pp. 1023-1031 . https://doi.org/10.2337/diabetes.54.4.1023 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11 beta-hydroxysteroid dehydrogenases (11 beta HSDs). 11 beta HSD1 activates GCs, while 11 beta HSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11 beta HSD1 produces visceral obesity and the metabolic syndrome in mice. To determine whether adipocytespecific inactivation of GCs protects against this phenotype, we created a transgenic model in which human 11 beta HSD2 is expressed under the control of the murine adipocyte fatty acid binding protein (aP2) promoter (aP2-h11 beta HSD2). Transgenic mice have increased 11 beta HSD2 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 gamma, 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. |
| Databáze: | OpenAIRE |
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