Retinol-binding protein 4 in human obesity.
Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral glucose tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4 concentrations were similar in the groups with higher and lower interstitial glucose levels. Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4.
Janke
Jürgen
J
Franz Volhard Clinical Research Center (Haus 129), Charité Campus Buch, Wiltbergstr. 50, 13125 Berlin, Germany.
Engeli
Stefan
S
Boschmann
Michael
M
Adams
Frauke
F
Böhnke
Jana
J
Luft
Friedrich C
FC
Sharma
Arya M
AM
Jordan
Jens
J
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015536:Down-Regulation; D005260:Female; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D006801:Humans; D017551:Microdialysis; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma
D051275:Glucose Transporter Type 4; C101326:RBP4 protein, human; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; C495692:SLC2A4 protein, human