Since evidence has appeared that tumor necrosis factor-alpha (TNF) is involved 
in the loss of body fat in the course of wasting diseases, a large number of 
studies have investigated the physiological role of this cytokine in adipose 
tissue. TNF treatment of several in vitro models of adipogenesis clearly showed 
that TNF is a potent inhibitor of adipose differentiation. This antiadipogenic 
property is accompanied by suppression of developmental and metabolic markers of 
fat cell differentiation, such as peroxisome proliferator-activated receptor 
(PPAR)-gamma2, lipoprotein lipase (LPL), glycerol-3-phosphate dehydrogenase 
(GPDH) and GLUT4. Moreover, TNF promotes lipolysis in mature adipocytes and, 
subsequently, a reversion of the adipocyte phenotype. Recent studies 
demonstrated that TNF directly interferes with the insulin signaling cascade at 
early steps and, thus, impairs insulin-stimulated glucose transport. Further 
progress in understanding the role of TNF in adipose tissue was made when 
endogenous TNF mRNA expression was demonstrated in adipose tissue. Obesity was 
found to represent a state of overexpression of the TNF system. Such findings 
support the hypothesis that TNF is a mediator of obesity-linked insulin 
resistance. However, this concept is mainly based on animal data and is so far 
only partially supported by studies in humans. Taken together, the results of a 
variety of experimental and clinical studies suggest that TNF may act as an 
important auto/paracrine regulator of fat cell function which serves to limit 
adipose tissue expansion, probably by inducing insulin resistance which may in 
turn cause metabolic disturbances. Elucidation of the molecular mechanisms of 
TNF production and action in adipose tissue may help to find new approaches for 
the treatment of insulin resistance in humans.