Selenium metabolism in cold-induced adaptive thermogenesis

摘要 本行政副刊建议家长资助DK128390的研究，旨在促进 具有西班牙血统的毕业后候选人Sydonie Swanson的研究和职业发展 寻求获得研究经验。家长基金的重点是确定硒循环在 棕色脂肪组织中硒蛋白酶GPX1和DIO2的调节及其循环机制 使用全身和棕色脂肪细胞特异性的在体内促进冷诱导的适应性产热 硒循环酶硒半胱氨酸裂解酶(SCLY)基因敲除小鼠模型。此管理 附录将通过追求以下研究目标来补充这些研究：1)确定 硒和SCLY在棕色脂肪细胞分化中的作用；2)确定是否对前脂肪细胞进行处理 加硒或SCLY活性调控硒蛋白Gpx4的表达和活性，影响 对上睑下垂的反应， 在分化的棕色脂肪细胞中，铁依赖的细胞死亡机制。这个 Sydonie的研究和职业发展计划侧重于培训技术人员(如组织学、显微镜、 基因编辑、生物信息学)和专业(例如，实验设计、科学写作和口头 演讲)在协作环境中的技能，这将提供强大的研究体验并有利于她 成功地纳入医务人员队伍。

ABSTRACT The studies proposed in this Administrative Supplement to parent grant DK128390 aim to promote the scientific research and career development of Sydonie Swanson, a Postbaccalaureate candidate with a Hispanic heritage seeking to gain research experience. The parent grant focuses on determining the role of selenium recycling in regulating selenoprotein enzymes GPX1 and DIO2 in brown adipose tissue and how the recycling mechanism contributes to cold-induced adaptive thermogenesis in vivo, using whole-body and brown adipocyte-specific knockout mouse models of the selenium recycling enzyme selenocysteine lyase (SCLY). This Administrative Supplement will complement these studies by pursuing these Research Aims: 1) To determine the role of selenium and SCLY in the differentiation of brown adipocytes; and 2) To determine if treatment of pre-adipocytes with selenium or the activity of SCLY controls the expression and activity of selenoprotein GPX4, impacting responses to ferroptosis, an iron-dependent cell death mechanism, in differentiated brown adipocytes. The Research and Career Development Plan for Sydonie focuses on training technical (e.g., histology, microscopy, gene editing, bioinformatics) and professional (e.g., experimental design, scientific writing, and oral presentations) skills in a collaborative environment that will provide a robust research experience and favor her successful inclusion in the medical workforce.