The role of AMPactivated protein kinase in the metabolic syndrome

Themetabolic syndrome was initially described in the 1920s and includes abnormalities such as glucose intolerance, insulin resistance, central obesity, dyslipidemia and hypertension. Although there is controversy as towhether it is truly a syndrome per se, the collection of symptoms it represents iswell recognised as a prevalent and major cardiovascular risk factor. The past two decades have witnessed a striking increase in the number of people with the metabolic yndrome worldwide. This increase is mainly associated with the epidemic increase in obesity and diabetes. About 20 to 30% of adults inWestern countries are now clinically classified as obese. However, the molecular mechanisms of obesity and the metabolic syndrome are as yet poorly understood. An increasing body of evidence has led to the hypothesis that themetabolic dysregulation of obesity and eventually the metabolic syndrome may involve AMP-activated protein kinase (AMPK), and that its dysregulation may play a critical role in the development of the multiple diseases associated with the metabolic syndrome, thus offering a target for therapy. AMPK has been investigated in obese animalmodels and in geneticallymodified animals,with increasing evidence supporting a role for AMPK in insulin sensitivity, the control of food intake and liver metabolism. Data from humans are unfortunately limited, andmainly focused on the role of AMPK in obesity and insulin resistance in human skeletalmuscle.A possible relation between AMPK and obesity aswell as insulin resistance,and a beneficial role of AMPK activating drugs have been shown.We await future studies regarding the relevance of the AMPK system and AMPK targeting drugs on human physiology and pathology.