Obesity is associated with an increased incidence of insulin resistance, 
dyslipoproteinemia, and hypercoagulability. In a more recently established 
hypothesis of body weight control and regulation of metabolism, the adipocyte 
secretes leptin and locally expresses TNF-alpha, the latter being responsible 
for the expression of metabolic cardiovascular risk factors. TNF-a mRNA 
expression and TNF-alpha protein are greatly increased in adipose tissue from 
obese animals and humans. Elevated TNF-alpha expression induces insulin 
resistance by downregulating the tyrosine kinase activity of the insulin 
receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha 
also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic 
lipolysis, and increases plasminogen activator inhibitor-1 content in 
adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary 
cytokine structure whose concentrations correlate with the amount of fat tissue. 
Increased leptin levels downregulate appetite and increase sympathetic activity 
and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose 
TNF-alpha expression and serum leptin levels and is associated with improved 
insulin sensitivity and lipid metabolism. Although exercise has also been shown 
to reduce leptin levels, an influence on TNF-a expression in adipocytes or 
muscle cells has not yet been demonstrated.