Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes.

Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific and factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA, encoded in mice by the gene . Whole-body deletion of in mouse is embryonically lethal, while targeted deletion of in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of in brown adipocytes (), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, mice maintain oxygen consumption and Ucp1 expression, with male mice accumulating more triglycerides in BAT than both female mice or controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in mice. Microarray analysis of BAT from mice revealed glutathione S-transferase alpha 3 () and ELMO domain containing 2 () as the transcripts most affected by the loss of . Male mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes and in their BATs. In summary, modest changes in the BAT of mice implicate a mild thyroid hormone dysfunction in brown adipocytes.