Endocrine Abstracts

The serum- and glucocorticoid-regulated kinase 1 (Sgk1) is a direct transcriptional target of glucocorticoids and is post-translationally activated by the insulin/IGF1 pathway. Distinct polymorphisms in the Sgk1 gene are associated with increased body weight and type 2 diabetes. Here we investigate the expression and regulation of Sgk1 in human obesity.

In both omental and subcutaneous human adipose tissue, Sgk1 expression is significantly increased in 20 obese patients compared to 20 age- and gender-matched controls. Sgk1 protein expression is mainly localised to adipose tissue macrophages. The expression of Sgk1 mRNA in subcutaneous adipose tissue correlates with waist circumference, weight, fat mass and HOMA insulin resistance index, as well as with circulating levels of C-reactive protein (CRP), leptin, interleukin 6 (IL6) and macrophage inflammatory protein 1α (MIP1α). Multiple regression analysis shows that waist circumference, weight, CRP and MIP1α independently predict Sgk1 expression in adipose tissue.

In peripheral blood mononuclear cells of eight obese patients compared to eight age- and gender-matched controls, Sgk1 expression is significantly higher in obese subjects. Monocyte-to-macrophage differentiation by phorbol 12-myristate 13-acetate (PMA) strongly induces Sgk1 mRNA expression in the THP1 monocytic cell line, parallel to increasing IL6 transcription. Lipopolysaccharide (LPS) significantly up-regulates Sgk1 mRNA expression in THP1 monocytes, but has no additional effect on PMA-stimulated Sgk1 in THP1 cells.

Taken together, we show increased Sgk1 expression in adipose tissue macrophages as well as circulating mononuclear cells of obese subjects compared to non-obese controls, presenting the first association between Sgk1 and obesity-related inflammation. In addition, our data identify PMA and LPS as novel regulators of Sgk1 in monocytic cells and suggest a role of Sgk1 in monocyte-to-macrophage differentiation. Further investigation of Sgk1 function in this context might be of therapeutical relevance in obesity-related inflammation and its comorbidities.