ADIPOSE-TISSUE OB MESSENGER-RNA EXPRESSION IN HUMANS - DISCORDANCE WITH PLASMA LEPTIN AND RELATIONSHIP WITH ADIPOSE TNF-ALPHA EXPRESSION

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposi ty. In 53 subjects covering a broad range of adiposity, we examined th e relationships between plasma leptin, adipose tissue ob mRNA levels, and adipose tissue TNF mRNA. There was a highly significant correlatio n between plasma leptin levels and every index of adiposity, In contra st, the relationship between ob mRNA levels and adiposity was weak. Ad ipose tissue from obese subjects demonstrated higher ob mRNA levels th an adipose tissue from lean subjects (lean: 0.49 +/- 0.05; obese 0.87 +/- 0.09 arbitrary units, P < 0.05). However, there was no significant corre lation between body fat and ob mRNA level. In addition, there w as no significant relationship between ob mRNA levels and plasma lepti n levels, which were measured in the same subjects. In addition to the measure of ob mRNA levels, adipose TNF mRNA levels were measured in 1 8 subjects. TNF mRNA levels varied with ob mRNA levels (r = 0.44, P = 0.06). These data show that plasma leptin levels are not directly rela ted to adipose tissue ob mRNA levels, suggesting posttranscriptional r egulation of leptin expression, either at the level of the adipocyte, or by alteration of plasma leptin degradation or clearance. In additio n, the parallel changes in ob and TNF mRNA in adipose tissue suggest t hat these two important factors in the defense against obesity may be regulated similarly.