title: Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity.
abstract: OBJECTIVE
  To examine the regulatory aspects of zinc-α2-glycoprotein (ZAG) association with obesity-related insulin resistance.
  
  
  METHODS
  ZAG mRNA and protein were analyzed in subcutaneous adipose tissue (AT) and circulation of lean, obese, prediabetic, and type 2 diabetic men; both subcutaneous and visceral AT were explored in lean and extremely obese. Clinical and ex vivo findings were corroborated by results of in vitro ZAG silencing experiment.
  
  
  RESULTS
  Subcutaneous AT ZAG was reduced in obesity, with a trend to further decrease with prediabetes and type 2 diabetes. ZAG was 3.3-fold higher in subcutaneous than in visceral AT of lean individuals. All differences were lost in extreme obesity. Obesity-associated changes in AT were not paralleled by alterations of circulating ZAG. Subcutaneous AT ZAG correlated with adiposity, adipocyte hypertrophy, whole-body and AT insulin sensitivity, mitochondrial content, expression of GLUT4, PGC1α, and adiponectin. Subcutaneous AT ZAG and adipocyte size were the only predictors of insulin sensitivity, independent on age and BMI. Silencing ZAG resulted in reduced adiponectin, IRS1, GLUT4, and PGC1α gene expression in primary human adipocytes.
  
  
  CONCLUSIONS
  ZAG in subcutaneous, but not in visceral AT, was markedly reduced in obesity. Clinical, cellular, and molecular evidence indicate that ZAG plays an important role in modulating whole-body and AT insulin sensitivity.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Balaz
authors.forename: Marek
authors.initials: M
authors.lastname: Vician
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Janakova
authors.forename: Timea
authors.initials: T
authors.lastname: Kurdiova
authors.forename: Martina
authors.initials: M
authors.lastname: Surova
authors.forename: Richard
authors.initials: R
authors.lastname: Imrich
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Majercikova
authors.forename: Adela
authors.initials: A
authors.lastname: Penesova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Vlcek
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
authors.forename: Vitazoslav
authors.initials: V
authors.lastname: Belan
authors.forename: Iwar
authors.initials: I
authors.lastname: Klimes
authors.forename: Juraj
authors.initials: J
authors.lastname: Olejnik
authors.forename: Daniela
authors.initials: D
authors.lastname: Gasperikova
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.forename: Barbara
authors.initials: B
authors.lastname: Ukropcova
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011236:Prediabetic State / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D052242:Adiponectin; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D029589:Seminal Plasma Proteins; D014157:Transcription Factors; D000090203:Zn-Alpha-2-Glycoprotein
keywords: extreme obesity; insulin sensitivity; mitochondria; subcutaneous and visceral adipose tissue; type 2 diabetes; zinc-α2-glycoprotein