Clinical diagnosis of metabolic syndrome 2. Lipotoxicity as a mechanism of the metabolic syndrome.

Visceral fat obesity plays an essential role in the clustering of atherosclerotic multiple risk factors in the metabolic syndrome. However, the mechanism by which visceral fat obesity causes clustering of glucose intolerance, high blood pressure, and dyslipidemia remains unknown. We have proposed a “lipotoxicity theory” as the mechanism behind metabolic syndrome and its consequences: an excess of free fatty acid predominantly causes impairment of insulin secretion and disturbance of insulin action in insulin-regulated organs. The Okinawa islands have long been well known as a region of longevity. However, the western lifestyle with its high-fat diet and motorization has permeated recent generations, causing the highest rate of visceral fat obesity and the metabolic syndrome in Japan. We found that subjects with the metabolic syndrome showed endothelial dysfunction, an underlying condition of cardiovascular events, on the basis of abdominal obesity. We now have expanded the steps of the process of the “lipotoxicity theory” to explain the possible mechanism of cardiovascular events in the metabolic syndrome: high-fat diet/over-eating → visceral fat obesity → the metabolic syndrome → endothelial dysfunction → cardiovascular events.