Research of the regulation of adipase mass through angiogenesis induced by the endothelin system

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Our Specific Aims of the research proposal and Results obtained were as follows:1. To elucidate the molecular mechanisms of ET-1 produced from endothelial cell in impaired angiogenesis in adipose tissue growth.Examination of oxygen consumption and respiratory quotient at 8 weeks of age showed no significant differences between WT and KO mice. There were no significant differences in locomotor activity and body temperature assessed by implanted radio frequency telemetry. Food consumption adjusted for mouse weight was not different between WT and KO mice. Vascular density in endothelin-1 deficient mice was decreased as compared to WT mice, indicating that retarded adipose mass growth in KO mice correlated with decreased vascular formation.2. To examine whether anti-obesity phenotype in ET-1 KO mice leads to the prevention for obesity-related disorders.We found that mice lacking endothelin-1 in vascular endothelial cells resist the development of diet-induced obesity, hypertension, and insulin resistance.3. To investigate the possibility whether the endothelin system could be a therapeutic target for obesity and the related disorders.ET-1 KO mice were mated with mice models of genetic obesity and insulin resistance to produce double mutant mice. We used two different kinds of obesity models, ob/ob and KKAy mice. We demonstrated that endothelin-1 has an important role for inducing inflammation in adipose tissue.