Figure 2.

The roles of TNF-α, adiponectin and NF-κB in the metabolic syndrome. [Adapted from Sonnenberg et al (41)] TNF-α secreted from adipose tissue in conjunction with circulating glucose, FFA and insulin stimulate NF-κB activation. This action is opposed by adiponectin (indicated by the broken line), also secreted from adipose tissue. Activation of the PPARγ pathway (for example by TZDs) has been shown to directly increase expression of adiponectin and reduce TNF-α. Further activation of NF-κB is induced through the resulting increase in inflammatory cytokines, adhesion molecules and oxidative stress, leading to the clinical manifestations of the metabolic syndrome. The metabolic syndrome is a constellation of cardiovascular risk factors that is associated with a trebling of risk of type 2 diabetes and a doubling of risk of cardiovascular disease. Several definitions have been proposed [80-83] leading to some confusion and differences in prevalence rates. The International Diabetes Federation have recently proposed a practical, globally applicable definition of the syndrome using waist circumference plus any two of raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting plasma glucose [84]. TNF-α – tumour necrosis factor alpha NF-κB – nuclear factor kappa beta FFA – free fatty acid LDL – low-density lipoprotein PPARγ – peroxisome proliferator activated receptor gamma TZD – thiazolidenedione