Obesity is frequently associated with insulin resistance and abnormal glucose 
homeostasis. Recent studies in animal models have indicated that TNF-alpha plays 
an important role in mediating the insulin resistance of obesity through its 
overexpression in fat tissue. However, the mechanisms linking obesity to insulin 
resistance and diabetes in humans remain largely unknown. In this study we 
examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 
control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha 
protein concentrations in plasma and in conditioned medium of explanted adipose 
tissue were measured by ELISA. Furthermore, the effects of weight reduction by 
dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were 
also analyzed in nine premenopausal obese women, before and after a controlled 
weight-reduction program. These studies demonstrated that obese individuals 
express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls 
(P < 0.001). Similar increases were also observed in adipose production of 
TNF-alpha protein but circulating TNF-alpha levels were extremely low or 
undetectable. A strong positive correlation was observed between TNF-alpha mRNA 
expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), 
an indirect measure of insulin resistance. Finally, body weight reduction in 
obese subjects which resulted in improved insulin sensitivity was also 
associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat 
tissue. These results suggest a role for the abnormal regulation of this 
cytokine in the pathogenesis of obesity-related insulin resistance.