Endocrine Abstracts

Serum and glucocorticoid-induced kinase 1 (Sgk1) is an early transcriptional target of glucocorticoids with antiapoptotic effects. Sgk1 becomes active after phosphorylation by growth factors such as insulin and IGF1 through the PI3 kinase/PDK1 pathway. Activated Sgk1 increases the cellular uptake of glucose by increasing the membrane abundance of glucose transporters GLUT1 and GLUT4. Here we present data on the expression and regulation of Sgk1 in adipose tissue using three different models: human obesity, diet-induced murine obesity and adipogenesis in 3T3-L1 cells.

Sgk1 gene expression was increased in both omental and subcutaneous adipose tissue of 20 morbidly obese patients when compared to 20 age- and sex-matched control subjects. Adipose tissue fractionation revealed a predominant expression of Sgk1 in adipose tissue macrophages and a very low expression in adipocytes. Similarly, high-fat diet-induced obesity in mice was associated with a significant upregulation of Sgk1 in adipose tissue, and predominantly in the stromal-vascular tissue. Sgk1 transcription in 3T3-L1 preadipocytes was strongly induced by dexamethasone and its phosphorylation was enhanced by insulin. Nevertheless, induction of adipogenesis in 3T3-L1 cells led to a progressive reduction in Sgk1 mRNA and protein levels. During adipogenesis, Sgk1 mRNA levels were in a strong negative correlation to the intracellular fat content and to the increase in PPARgamma mRNA. Overexpression of Sgk1 in 3T3-L1 adipocytes did not influence PPARgamma levels, while the addition of rosiglitazone decreased Sgk1 transcription.

In summary we conclude that Sgk1 expression is increased in adipose tissue macrophages in both human and murine obesity, but downregulated in adipocytes during adipogenesis and after PPARgamma activation. The reduced Sgk1 levels in adipocytes may be linked to increased insulin resistance, as Sgk1 increases glucose uptake via upregulating the membrane abundance of glucose transporters. In parallel, the increased Sgk1 expression in macrophages points towards a potential role in adipose tissue inflammation.