regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue调节脂肪生成的糖皮质激素和胰岛素在人类脂肪组织.pdfVIP

Regulation of Lipogenesis by Glucocorticoids and Insulin in Human Adipose Tissue Laura L. Gathercole, Stuart A. Morgan, Iwona J. Bujalska, David Hauton, Paul M. Stewart, Jeremy W. Tomlinson* Centre for Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom Abstract Patients with glucocorticoid (GC) excess, Cushing’s syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11b-Hydroxysteroid dehydrogenase type 1 (11b-HSD1) and we have hypothesized that 11b-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc) and omental (om) adipocytes. Across adipocyte differentiation, lipogenesis increased whilst b-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of b-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM) of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11b-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability t