Hepatic Glucocorticoid Receptor Plays a Greater Role Than Adipose GR in Metabolic Syndrome Despite Renal Compensation
| Autor: | Irina Hutson, Charles A. Harris, Sandip K. Bose |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Adipose tissue 030209 endocrinology & metabolism Biology Kidney Mice 03 medical and health sciences chemistry.chemical_compound Receptors Glucocorticoid 0302 clinical medicine Endocrinology Glucocorticoid receptor Insulin resistance Internal medicine medicine Animals Glucose homeostasis Triglycerides Metabolic Syndrome Mice Knockout Glycogen Gluconeogenesis Kidney metabolism Lipid metabolism Lipid Metabolism medicine.disease 030104 developmental biology Adipose Tissue Liver chemistry Body Composition Insulin Resistance Glucocorticoid Research Article medicine.drug |
| Zdroj: | Endocrinology. 157:4943-4960 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2016-1615 |
| Popis: | Exogenous glucocorticoid administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia, and hypertension, a constellation of findings known as Cushing’s syndrome. These effects are mediated by the glucocorticoid receptor (GR). Because GR activation in liver and adipose has been implicated in metabolic syndrome (MS), we wanted to determine the role of GR in these tissues in the development of MS. Because GR knockout (KO) mice (whole-body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue-specific (liver or adipose) GRKO mice using cre-lox technology. Real-time PCR analysis of liver mRNA from dexamethasone-treated wildtype (WT) and liver GRKO mice indicated that hepatic GR regulates the expression of key genes involved in gluconeogenesis and glycogen metabolism. Interestingly, we have observed that liver-specific deletion of GR resulted in a significant increase in mRNA expression of key genes involved in gluconeogenesis and glycogen metabolism in kidney tissue, indicating a compensatory mechanism to maintain glucose homeostasis. We have also observed that GR plays an important role in regulating the mRNA expression of key genes involved in lipid metabolism. Liver GRKO mice demonstrated decreased fat mass and liver glycogen content compared with WT mice administered dexamethasone for 2 weeks. Adipose-specific deletion of GR did not alter glucose tolerance or insulin sensitivity of adipose GRKO mice compared with WT mice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms. |
| Databáze: | OpenAIRE |
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