Hepatic glucocorticoid receptor plays a greater role than adipose gr in metabolic syndrome despite renal compensation

Sandip K. Bose, Irina Hutson, Charles A. Harris

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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). BecauseGRactivation 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 liverspecific 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 adiposeGRKOmice compared withWTmice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasonetreated mice, whereas adipose GR plays a little role in these paradigms.

Original languageEnglish
Pages (from-to)4943-4960
Number of pages18
JournalEndocrinology
Volume157
Issue number12
DOIs
StatePublished - Dec 2016

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