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SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet‐induced obesity
Author(s) -
Scott Takara A.,
Babayeva Oguljahan,
Banerjee Saswati,
Zhong Wei,
Francis Sharon C.
Publication year - 2016
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21425
Subject(s) - resistin , sgk1 , medicine , endocrinology , adipokine , adipose tissue , vascular smooth muscle , phosphorylation , adipocyte , biology , leptin , obesity , glucocorticoid , microbiology and biotechnology , smooth muscle
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.