内臓脂肪症候群におけるインスリン抵抗性と動脈硬化

Abstract

In recent years, multiple risk factor syndromes, including Syndrome X, the deadly quartet syndrome, and visceral fat syndrome have been noted as common condition for the development of coronary artery disease (CAD). Although these syndromes are often accompanied by insulin resistance, its pathogenesis have not been elucidated.We have investigated the relationship between body fat composition and obesity-linked disorders and found the accumulation of intra-abdominal visceral fat is closely related to glucose intolerance, hypertension, hyperlipidemia, and insulin resistance determined by steady-state plasma glucose level in obese and even in non-obese people. Thus, visceral fat accumulation is the feasible condition for the development of insulin resistance and multiple coronary risks.Although it is speculated that the multiple features in “multiple risk factor syndrome” are caused by insulin resistance, its molecular pathophysilogy has not been clarified. Recently it has been revealed that adipose tissue secretes various biologically active molecules. To clarify the molecular basis of hyperlipidemia, we analyzed expression of the genes for VLDL synthesis in animal model of visceral fat syndrome. Portal FFAs were elevated according to visceral fat accumulation even at early stage when insulin resistance has not manifested. Hepatic acyl-CoA synthetase and microsomal triglyceride transfer protein mRNA levels were upregulated compared to their lean littermates. These results suggested that enhancement of expression of these genes may be one of the mechanisms for hyperlipidemia in visceral fat accumulation. Type 1 plasminogen activator inhibitor (PAI-1) has a regulatory role in fibrinolytic process. Plasma PAI-1 levels were significantly correlated with the visceral fat area in obese (r=0.32, p<.02) and even in non-obese subjects (r=0.38, p<.02) but not with the subcutaneous fat area. PAI-1mRNA was detected in human and rodent adipose tissues and increased to 10-fold in visceral fat after making of VMH lesions, remaining unchanged in the subcutaneous fat, suggesting that secretion of PAI-1 from visceral fat may be responsible for elevated plasma PAI-1 and have a role in the development of vascular diseases in visceral fat syndrome.These results suggested that visceral fat accumulation causes multiple coronary risks through the insulin resistance or independently by the molecules secreted from accumulated visceral fat.