RESUMEN
OBJECTIVE: Enhanced serum and glucocorticoid-inducible kinase 1 (SGK1) activity contributes to the pathogenesis of vascular disease. This study evaluated SGK1 modulation in vascular smooth muscle cells by the adipokine resistin and in aortic tissue in a murine model of diet-induced obesity (DIO). METHODS: Modulation of SGK1 by resistin was assessed in human aortic smooth muscle cells (HAoSMC) in vitro by quantitative RT-PCR and Western blot analyses. To induce the lean or obese phenotype, mice were fed a 10 kcal% low-fat or 60 kcal% high-fat diet, respectively, for 8 weeks. Upon study completion, plasma resistin was assessed and aortic tissue was harvested to examine the effect of DIO on regulation of SGK1 in vivo. RESULTS: Resistin increased SGK1 mRNA, total protein abundance, and its activation as determined by phosphorylation of its serine 422 residue (pSGK1) in HAoSMC. Resistin-mediated SGK1 phosphorylation was dependent upon phosphatidylinositol-3-kinase and Toll-like receptor 4. Furthermore, inhibition of SGK1 attenuated resistin-induced proliferation in HAoSMC. DIO led to up-regulation of total SGK1 protein levels and pSGK1 in association with increased plasma resistin. CONCLUSIONS: These data suggest that high levels of resistin observed during obesity may activate SGK1 in the vasculature and contribute to the development of obesity-related vascular disease.