The significance of adipocvte-specific glycerol channel, aquaporin adipose for life-style related diseases.

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Metabolic syndrome clusters insulin resistance, elevated blood pressure and dyslipidemia, and is a common cause of cardiovascular diseases in the world. The molecular basis of the metabolic syndrome, however, remained unclear. Accumulation of intra-abdominal adipose tissue caused by overnutrition and physical inactivity locates upstream of the metabolic syndrome. Adipose tissue had been regarded as a simple energy storage organ. Our team clarified the tissue is a huge endocrine organ to express genes for various bioactive substances, and concepualized as 'adipocytokines'. Through the study, we discovered various novel adipocyte-expressed genes. In this study, we focused adipocytokines to clarify molecular mechanism of the metabolic syndrome. Adiponectin is an adipocyte-derived protein present abundantly in plasma. Plasma level of adiponectin is decreased in subjectes with visceral fat. Blood pressure levels of adiponectin deficient mice were almost normal. When the mice were fed with h … More igh salt-diet, their blood pressure levels were elevated. The expression of endogenous nitric oxide synthetase (eNOS) and prostacyclin synthetase was augmented in the aorta of the KO mice. Adenovirus-mediated supplementation of adiponectin lowered blood pressure level of adiponectin KO mice. The effect was cancelled by the administration of L-NAME, which is a specific inhibitor of eNOS, suggesting salt-sensitive hypertension in adiponectin deficiency is caused by lack of NO and vascular endothelial cell dysfunction. A series of studies revealed that adiponectin deficiency worsened cardiac reperfusion injury, cardiac hypertrophy and vascular thrombosis. Clinical studies demonstrated that decreased plasma adiponectin (hypoadiponectinemia) is related to complexity of coronary artery lesion, coronary spasm and peripheral artery disease. Hypoadiponectinemia increased a risk of cardiovascular events in type 2 diabetic subjects and adverse cardiac events after myocardial infarction, also related to cardiovascular risks of the patients with chronic renal disease. Improvement of life-style including cessation of smoking is important to correct hypoadiponectinemia. We demonstrated blockade of adipose angiotensin receptor decreased reactive oxygen species in adipose tissue and recovered plasma adiponectin level. We also showed a novel mechanism of obesity through the analyses of the mice with lack of aquaporin 7, which we had demonstrated as a glycerol channel molecule in adipocyte. These basic and clinical studies will give an impact on the research field of the metabolic syndrome. Less