Term Paper on "Pathophysiology of the Metabolic Syndrome"

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Obesity is considered a significant factor in metabolic syndrome, especially abdominal obesity. The adipose tissue releases factors which exacerbate the cardiovascular risk factors, such as nonesterfied fatty acids, cytokines and adiponectin. These elements overload the muscle and liver with lipid, increasing insulin resistance. Adiponectin and cytokine excess may cause a proinflammatory state and may correlate to a prothrombotic state, both of which can increase incidence of cardiovascular disease.

Insulin resistance may be even more important than obesity in the pathogenesis of metabolic syndrome. Insulin resistance rises with higher levels of body fat. Insulin resistant muscle is overloaded with lipid, thus causing a diversion of lipid to the liver and atherogenic plaque. Triglyceride levels are elevated. Insulin resistance is also thought to be associated with increased blood pressure, although the actual mechanism is not entirely clear.

Several elements have been associated with the pathogenesis of metabolic syndrome. These factors include:

Atherogenic dyslipidemia

Apolipoprotein B

Small low density lipoprotein

Low high density lipoprotein

Inflammatory cytokines also appear to play a part in the pathophysiology of metabolic syndrome. Tumor necrosis factor a (TNF-a) and interleukin (IL)-6 are both produced in large amounts by adipose tissue. Proinflammatory cytokines increase hepatic lipogensis and may also elicit a systemic acute-phase response (Manson, et al., 2005). The TNF impairs insulin stimulated glucose uptake in cells and also decreases lipoprotein lipase activity (lipoprotein lipase is an enzyme which hydrolyzes lipoproteins like chylomicrons, into smaller fat units). Acute phase reactants like fibrinogen, white blood cells and plasminogen activator inhibitor-1 levels are also found to be associated with metabolic syndrome (Juahan-Vague & Alessi, 1997).

C-reactive protein (CRP) levels correlate with Body Mass Index and other features associated with metabolic syndrome. CRP is a very sensitive acute phase reactant. These inflammatory mediators are doubly significant since inflammation appears to be associated with the generation of atherosclerotic plaque. Different pathophysiologic factors appear to be associated with different components of the syndrome. Grouping of the risk factors tend to be associated with a higher risk of development of Coronary Heart Disease (CHD) and the presence of three or more of the metabolic risk… READ MORE