Selenium metabolism in cold-induced adaptive thermogenesis

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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.