title: SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet-induced obesity.
abstract: 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.
authors.affiliation: Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Takara A
authors.initials: TA
authors.lastname: Scott
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Oguljahan
authors.initials: O
authors.lastname: Babayeva
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Saswati
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia, USA.|Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Francis
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D052243:Resistin / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C499624:RETN protein, human; D052243:Resistin; D051197:Toll-Like Receptor 4; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase
references.citation: Cell Metab. 2014 Mar 4;19(3):484-97
references.pmid: 24606903
references.citation: Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):547-57
references.pmid: 25614279
references.citation: Diabetes Res Clin Pract. 2013 Oct;102(1):35-42
references.pmid: 24035040
references.citation: Am J Physiol Cell Physiol. 2009 Dec;297(6):C1466-76
references.pmid: 19828833
references.citation: Expert Opin Ther Targets. 2009 Nov;13(11):1303-11
references.pmid: 19764891
references.citation: J Biol Chem. 2009 Feb 13;284(7):4073-89
references.pmid: 19088076
references.citation: J Biomed Sci. 2014 Jun 14;21:59
references.pmid: 24929539
references.citation: Cell Tissue Res. 2013 Jan;351(1):161-74
references.pmid: 23086480
references.citation: Dev Dyn. 2010 Aug;239(8):2149-60
references.pmid: 20568246
references.citation: Circ Res. 2006 Mar 31;98(6):828-36
references.pmid: 16484615
references.citation: Heart Vessels. 2007 Nov;22(6):416-22
references.pmid: 18044001
references.citation: J Cell Physiol. 2011 Aug;226(8):2181-8
references.pmid: 21520070
references.citation: Circulation. 2004 Nov 23;110(21):3335-40
references.pmid: 15545519
references.citation: Int J Obes (Lond). 2015 Jul;39(7):1143-50
references.pmid: 25809829
references.citation: Mol Cell Endocrinol. 2013 Feb 5;366(1):108-16
references.pmid: 23267839
references.citation: Biochem J. 2008 Dec 15;416(3):375-85
references.pmid: 18925875
references.citation: Curr Opin Nephrol Hypertens. 2009 Sep;18(5):439-48
references.pmid: 19584721
references.citation: Cell Biol Int. 2007 Aug;31(8):831-5
references.pmid: 17344072
references.citation: Thromb Haemost. 2015 Mar;113(3):553-66
references.pmid: 25338625
references.citation: Biochem Med (Zagreb). 2015 Jun 05;25(2):242-51
references.pmid: 26110037
references.citation: Circ Res. 2010 Nov 12;107(10 ):1265-74
references.pmid: 20884880
references.citation: Nature. 2001 Jan 18;409(6818):307-12
references.pmid: 11201732
references.citation: Leukemia. 2011 Jun;25(6):960-7
references.pmid: 21455214
references.citation: Eur Heart J. 2008 Dec;29(24):2959-71
references.pmid: 18775919
references.citation: Clin Sci (Lond). 2011 Feb;120(3):121-9
references.pmid: 20795947
references.citation: EMBO J. 1999 Jun 1;18(11):3024-33
references.pmid: 10357815
references.citation: Am J Physiol Renal Physiol. 2006 Dec;291(6):F1264-73
references.pmid: 17003223
references.citation: Clin Lab. 2003;49(11-12):571-6
references.pmid: 14651328
references.citation: Cardiovasc Res. 2006 Jan;69(1):76-85
references.pmid: 16271710
references.citation: Diabetologia. 2014 Jun;57(6):1209-18
references.pmid: 24623101
references.citation: Int J Biochem Cell Biol. 2014 May;50:29-37
references.pmid: 24508784
references.citation: Horm Mol Biol Clin Investig. 2015 Apr;22(1):19-26
references.pmid: 25941914
references.citation: Cell Signal. 2014 Dec;26(12 ):2765-72
references.pmid: 25152363
references.citation: J Cell Mol Med. 2010 Jun;14(6B):1419-31
references.pmid: 19754671
references.citation: Physiol Rev. 2006 Oct;86(4):1151-78
references.pmid: 17015487
references.citation: Br J Pharmacol. 2012 Feb;165(3):622-32
references.pmid: 21545576
references.citation: J Clin Invest. 2009 Sep;119(9):2634-47
references.pmid: 19690389