1506-P: Effect of Beta-Agonist Treatment on Selenium Metabolism in Differentiated Brown Adipocytes

Abstract

Selenium (Se) is an essential trace element important to several body processes such as metabolism, thyroid function, and curbing of oxidative stress. Se is utilized as the amino acid known selenocysteine (Sec), decomposed by the enzyme selenocysteine lyase (Scly). Selenoproteins have a broad range of functions, including protecting against lipid peroxidation and apoptosis, metabolic dysregulation such as glucose intolerance, and other immune responses. In brown adipocytes, the selenoprotein glutathione peroxidase 4 (GPX4) plays a key role in lipid peroxidation which in turn allows for proper thermogenic responses triggered by adrenergic signals. GPX4 removes toxic lipid peroxides by converting them into non-toxic alcohol and water. When Se levels are insufficient in brown adipocytes, the selenoprotein GPX4 may be downregulated, leading cells to accumulate a lethal amount of lipid peroxidases and triggering ferroptosis, a type of cell death. Ferroptosis activation, in turn, negatively impact pathways dependent on adrenergic responses in brown adipocytes, such as thermogenesis activation. To determine how Se levels regulate the expression of Scly and GPX4 upon treatment with adrenergic agonist in differentiated PAZ6 brown adipocytes. Human PAZ6 pre-adipocytes were differentiated for 21 days, then treated with insufficient (20 nM), adequate (80 nM), and high sodium selenite (160 nM) levels for 48h. Differentiated brown adipocytes were also treated with 1 μM CL-316243, a β3-adrenergic receptor agonist, for 24h after selenite treatment. Cells were then harvested for qPCR and Western blot analysis. Differentiated PAZ6 cells had an increase in UCP1 expression, a marker of brown adipocytes. Upon Se treatment, both Scly and GPX4 expression were unchanged in PAZ6 cells. Treatment with β3-adrenergic receptor agonist also did not affect the expression levels of both proteins. In differentiated brown adipocytes, expression of Scly and GPX4 is not dependent on Se nor β-agonist signals. Disclosure S.Swanson: None. Funding National Institutes of Health (R01DK128390)