Metabolic Syndrome in Humans - Aetiology and Treatment

The global epidemic of obesity and its associated complications has hastened the need with which we must understand both the patho-physiological process that contributes to its development, and also the urgency with which we need therapeutic solutions that offer clinically meaningful and sustained weight loss. Dysregulation of the hypothalamo-pituitary adrenal axis has been observed in patients with obesity and the metabolic syndrome; however, circulating cortisol levels are not elevated. At a tissue specific level, in liver, muscle and adipose tissue, active glucocorticoid, cortisol is regenerated from inactive cortisone by the enzyme 11β-Hydroxysteroid dehydrogenase type 1 (11β- HSD1) and is thus able to amplify local glucocorticoid action. Tissue-specific dysregulation of 11β-HSD1 has been proposed as a pathogenic mechanism in obesity and the metabolic syndrome.

There is clear evidence as to the beneficial impact of exercise upon health, in particular cardiovascular health, in normal weight and obese individuals as well as those with type 2 diabetes. Exercise training is associated with decreased cardiovascular risk, less atherogenic lipid profiles, improvements in blood pressure and insulin sensitivity. Importantly, the decline in insulin sensitivity once exercise training is discontinued exemplifies the need for permanent lifestyle modification and regular exercise. [...]