Molecular pathogenesis and mechanism of vidseral obesity

点击翻译按钮获取中文摘要

Obesity, especially accumulation of intra-abdomicl visreal fat is a common basis of the development of various life-style-related diseases including diabetes mellitus, dyslipoproteinemia, hypertension and atherosclerotic vascular diseases. In he current study, we investigted the biological functions of adipose tissue and molecular pathogenesis of obesity-related diseases. We have demonstrated that adipose tissue is not solely an energy-storing organ but also an endocrine organ producing and secreting a variety of biological substances in the circulation. Among them, hypersecretion of plasminogen activator inhibitor type 1 and heparin binding EGF-like growth factor form intra-abdominal adipose tissue were considered to affect the function and metabolism of vascular walls directly and to play roles in the development of vascular diseases.In this study, we especially focused on a novel collagen-like plasma protein, adiponectin and a member of aquaporin family, aquaporin adipose (AQPap). A … More dionectin was specifically and abundantly synthesized in adipose tissue. The protein was present in the circulation with the concentration of 5-10μg/ml. Different from thecases of PAI-1 and HB-EGF, plasma adiponectin concentrations were markedly reduced in obesity, especially in visceral obesity. When the vascular endothelium was injured in rats, adiponectin was observed in the injured vascular wall. The protein suppressed monocyte-adhesion to endothelial cells and proliferation of vascular smooth muscle cells, which are the initial changes of atherosclerotic lesion. By the analysis of adiponectin gene, we found missense mutation in subjects with coronary artery disease. These data suggest that adiponectin has potential protective activity against atherosclerotic vascular diseases and hypoadiponectin-emia found in visceral obesity may play a role in the development of atherosclerotic diseases.We investigated the function of AQPap in adipocytes. Several lenes of enidences supported that AQPap works as a glycerol channel in adipocytes; 1) AQPap exhibited glycerol permeability when it was expressed in oocytes, 2) expression of AQPap mRNA was induced by fasting in which glycerol release from the cell was activated, 3) glycerol release from the cells was reduced by mercuty ion, which inhibits the function of AQP family. Expression of AQPap was augumented and glycerol concentration in adipose tissue was increased in obese mice. In visceral fat accumulation, large amount of glycerol were drained into the liver via portal vein, may disturb glucose metabolism in liver.In conclusion, the expressions of various adipose-specific genes are altered in visceral obesity. These might contribute to the development of disorders in visceral obesity. Less