Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women

Insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) expression may provide an indirect reflection of the capacity of adipocytes to respond to insulin stimulation. We examined messenger RNA (mRNA) expression of these genes in omental and subcutaneous adipose tissue of women. Paired omental and subcutaneous adipose tissue samples were obtained from 36 women (age, 47 ± 5 years; body mass index, 28.0 ± 5.4 kg/m²) undergoing gynecologic surgeries. Total adiposity and visceral adiposity were assessed by dual-energy x-ray absorptiometry and computed tomography. The GLUT4 and IRS-1 mRNA expression levels were both significantly higher in subcutaneous compared with omental adipose tissue. A negative correlation was observed between body fat percentage and subcutaneous adipose tissue GLUT4 (r = −0.39, P < .05) and IRS-1 (r = −0.30, P < .08) mRNA abundance. However, in omental fat, only GLUT4 mRNA was inversely associated with body fat percentage (r = −0.53, P < .001). Moreover, the homeostasis model assessment of insulin resistance index was associated with mRNA expression of subcutaneous GLUT4 (r = −0.56, P < .001), subcutaneous IRS-1 (r = −0.51, P < .01), and omental GLUT4 (r = −0.54, P < .001), but not omental IRS-1. Interestingly, plasma adiponectin was only associated with subcutaneous GLUT4 (r = 0.48, P < .01) and IRS-1 (r = 0.48, P < .05) mRNA expression. The GLUT4 protein, unlike mRNA expression, was higher in omental than in subcutaneous adipose tissue. However, abdominal obesity-related differences in protein or mRNA expression were similar. Omental IRS-1 expression was low and unaffected by visceral obesity. In contrast, omental and subcutaneous GLUT4 as well as subcutaneous IRS-1 were reduced in visceral obesity. This divergent pattern of expression may reflect a lower capacity of omental adipose tissue to respond to insulin stimulation at all adiposity levels.