The effects of glucocorticoids on the expression of gluconeogenic and lipogenic enzymes in a rodent model of Cushing’s syndrome

Francesca Lolli; Mirjam Christ-Crain; Blerina Kola; Csaba Fekete; Gábor Wittman; Ashley B Grossman; Márta Korbonits

P255

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Endocrine Abstracts (2007) 14 P255

ECE2007 Poster Presentations (1) (659 abstracts)

The effects of glucocorticoids on the expression of gluconeogenic and lipogenic enzymes in a rodent model of Cushing’s syndrome

Francesca Lolli ¹ , Mirjam Christ-Crain ¹ , Blerina Kola ¹ , Csaba Fekete ² , Gábor Wittman ² , Ashley B Grossman ¹ & Márta Korbonits ¹

Err

Author affiliations

¹Department of Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary School of Medicine, London, United Kingdom; ²Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gluconeogenesis in adipose tissue and liver.

Methods: Rats were implanted with corticosterone-containing pellets, and consumed chow and 30% sucrose for two weeks according to a well-established model of glucocorticoid excess. Animals implanted with cholesterol (placebo) pellets consuming sucrose or saline only served as controls. RNA was extracted from mesenteric and subcutaneous adipose tissue and liver. Gene expression was analyzed by reverse transcription followed by real time quantitative PCR with primers specific for phosphoenolpyruvate carboxykinase (PECPK), sterol regulatory element-binding protein (SREBP1c and SREBP2), fatty acid synthase (FAS), glucose-6-phospatase (G6P) and β-actin as housekeeping gene.

Results: In the mesenteric adipose tissue GC significantly increased PEPCK mRNA expression (P=0.01), SREBP1c and FAS mRNA expression (P=0.02 and P=0.035, respectively). No significant changes were observed in subcutaneous fat tissue. In the liver GC significantly increased FAS mRNA expression (P<0.0001) and decreased PEPCK mRNA (P=0.027), without changes in the expression of G6P or SREBP1c.

Conclusions: GC increase the expression of lipogenic and glyceroneogenic genes in visceral adipose tissue and this could explain the increased fat storage observed in the visceral fat of Cushing’s syndrome. The changes in the liver would lead to increased fat deposition with less gluconeogenesis, and this was reflected in the massive fatty liver observed experimentally. We suggest that there may be a common factor leading to these changes secondary to the excess of glucocorticoids.