| Summary: | 碩士 === 國立交通大學 === 分子醫學與生物工程研究所 === 104 === The metabolic syndrome has become one of the major worldwide epidemics because of increasing obesity, and sedentary lifestyles. An overaction of renin angiotensin system (RAS) has been implicated in metabolic syndrome. Our previous studies showed that mice lacking renin (Ren1c −/−) are insulin sensitive and resist diet-induced obesity. Moreover, heat generation (thermogenesis), which is predominantly produced by brown adipose tissues (BAT) and has the ability to enhance energy expenditure, is significantly increased in Ren1c −/− mice. Plasma angiotensin II (Ang II) can not be detected in Ren1c −/− mice, and Ang II is known for inducing reactive oxygen species (ROS) which can cause mitochondrial damage, decrease fatty acid oxidation and induce mitochondrial dynamics needed for maintaining mitochondrial quality. Therefore, we hypothesized that inhibition of Ang II resists diet-induced obesity by enhancing thermogenesis in BAT via regulating fatty acid oxidation and mitochondrial dynamics. In vitro, our study indicated that Ang II significantly decreased uncouple protein 1 (UCP1) gene expression. After treating Ang II type 1 blocker losartan, UCP1 gene expression was restored. Furthermore, Ang II reduced fatty acid oxidation and increased mitochondrial fission while we treated mitochondrial fission protein Drp-1 inhibitor mdivi-1 resulting in abolishing Ang II effects, and restored mitochondrial function. Therefore, our data suggested that Ang II regulates BAT thermogenesis and fatty acid oxidation via increased mitochondrial fission.
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