Subcutaneous adipose tissue zinc‐α2‐glycoprotein is associated with adipose tissue and whole‐body insulin sensitivity

• Published in: Obesity (Silver Spring, Md.) Md.), 2014-08, Vol.22 (8), p.1821-1829
• Main Authors: Balaz, Miroslav, Vician, Marek, Janakova, Zuzana, Kurdiova, Timea, Surova, Martina, Imrich, Richard, Majercikova, Zuzana, Penesova, Adela, Vlcek, Miroslav, Kiss, Alexander, Belan, Vitazoslav, Klimes, Iwar, Olejnik, Juraj, Gasperikova, Daniela, Wolfrum, Christian, Ukropcova, Barbara, Ukropec, Jozef
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adiponectin - genetics; Adiponectin - metabolism; Adiposity - genetics; Adult; Diabetes Mellitus, Type 2 - metabolism; extreme obesity; Female; Gene Expression; Gene Silencing; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Humans; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Insulin Resistance - genetics; insulin sensitivity; Intra-Abdominal Fat - metabolism; Male; Middle Aged; mitochondria; Obesity - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Prediabetic State - metabolism; RNA, Messenger - metabolism; Seminal Plasma Proteins - genetics; Seminal Plasma Proteins - metabolism; subcutaneous and visceral adipose tissue; Subcutaneous Fat - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; type 2 diabetes; zinc‐α2‐glycoprotein
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.20764

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.