Physiological relationships of uncoupling protein-2 gene expression in human adipose tissue in vivo

The physiological significance of changes in uncoupling protein-2 (UCP-2) g ene expression is controversial. In this study me investigated the biochemi cal and functional correlates of UCP-2 gene expression in sc abdominal adip ose tissue in humans in vivo. UCP-2 messenger ribonucleic acid expression w as quantified by nuclease protection in adipose tissue from lean and obese humans in both the fasting and postprandial states. Plasma fatty acids, ins ulin, and leptin were all determined in paired samples from the superficial epigastric vein and radial artery, and local production rates were calcula ted from Xe-133 washout. In the fasting state UCP-2 expression correlated i nversely with body mass index (r = -0.45; P = 0.026), percent body fat (r = -0.41; P = 0.05), plasma insulin (r = -0.47; P = 0.02), epigastric Venous fatty acids (r = -0.45; P = 0.04), and leptin (r = -0.50; P = 0.018). UCP-2 expression remained inversely related with plasma leptin after controlling for percent body (r = -0.45; P = 0.038). At 2 or 4 h postprandially, there were no significant relationships between UCP-2 expression and biochemical parameters. In conclusion, 1) UCP-2 messenger ribonucleic acid expression in sc adipose tissue is inversely related to adiposity and independently li nked to local plasma leptin levels; and 2) UCP-2 expression is not acutely regulated by food intake, insulin, or fatty acids. Reduced UCP-2 expression may be a maladaptive response to sustained energy surplus and could contri bute to the pathogenesis and maintenance of obesity.