@phdthesis{oai:oist.repo.nii.ac.jp:00001343,
 author = {Takaoka, Shohei},
 month = {2020-04-02, 2020-04-02},
 note = {Gene expression of eukaryotes is regulated by various processes including mRNA degradation. Dysregulation of mRNA degradation is now considered to be a possible cause of various disease including cancer, neurodegenerative disease, diabetes, and obesity. 5’ - 3’ exoribonuclease Xrn1 functions at the last step of mRNA degradation. Recent studies showed that Xrn1 forms specific cytoplasmic messenger ribonucleoprotein (mRNP) granules in postsynapse to regulate local translation. However, there are no physiological studies that have investigated the function of Xrn1 in the brain. Therefore, I generated forebrain specific Xrn1 knockout mice for the first time and analyzed their phenotype. Interestingly, the knockout mice showed obesity and hyperphagia. Energy homeostasis is regulated by various organs including central nervous systems and peripheral metabolic tissues such as liver, pancreas, and adipose tissues, thus the development of obesity is often caused by the dysregulation of inter-organ communication. In response to metabolic cues, peripheral tissues produce hormones such as insulin and leptin. The hypothalamus sense changes in circulating blood glucose, insulin, and leptin and integrate those cues to maintain metabolic homeostasis. Blood analysis showed that the conditional Xrn1 knockout mice were hyperglycemic, hyperleptinemic, and hyperinsulinemic. Consistent with the above phenotype, I observed dysregulated expression of appetite and energy homeostasis related genes in the hypothalamus of the knockout mice. These data suggest that Xrn1 is required for the regulation of appetite and energy homeostasis related gene expression in the hypothalamus, and thus Xrn1 plays a role in energy expenditure and control of obesity.},
 school = {Okinawa Institute of Science and Technology Graduate University},
 title = {エネルギー消費と肥満の制御における5 '-3'エキソリボヌクレアーゼXrn1の役割},
 year = {}
}