Abstract
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 cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA[Ser]Sec, encoded in mice by the gene Trsp. Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp 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 Trsp in brown adipocytes (Trspf/f-Ucp1-Cre+/−), 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, Trspf/f-Ucp1-Cre+/− mice maintain oxygen consumption and Ucp1 expression, with male Trspf/f-Ucp1-Cre+/− mice accumulating more triglycerides in BAT than both female Trspf/f-Ucp1-Cre+/− mice or Trspf/f 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 Trspf/f-Ucp1-Cre+/− mice. Microarray analysis of BAT from Trspf/f-Ucp1-Cre+/− mice revealed glutathione S-transferase alpha 3 (Gsta3) and ELMO domain containing 2 (Elmod2) as the transcripts most affected by the loss of Trsp. Male Trspf/f-Ucp1-Cre+/− mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trspf/f-Ucp1-Cre +/− mice implicate a mild thyroid hormone dysfunction in brown adipocytes.
Highlights
brown adipose tissue (BAT) expression of the Trsp tRNA was reduced by ~60% (Figure 1b), with remaining Trsp expression possibly reflecting its presence in other cell types within the tissue
Our model was characterized by targeted deletion of The the product gene Trsp in Trsp gene, brown adipocytes, which are the primary cell type of BAT
Is responsible for carrying out the synthesis of selenoproteins, including deiodinase type 2 (Dio2), Dio2 upregulation is promoted by thyroid hormone and is considered a primary a regulator of cold-induced adaptive thermogenesis in BAT
Summary
Selenoproteins are a small group of proteins containing the micronutrient selenium in their molecule. These proteins are involved in redox reactions that can reduce oxidative stress, activate thyroid hormones, and act on endoplasmic reticulum-associated degradation of misfolded proteins. Selenoproteins exert a profound effect in several aspects of health, including the pathophysiology of different types of cancer [1,2,3], autoimmune diseases [4], irritable bowel syndrome [5], type 2 diabetes [6,7], and thyroid disorders [8,9]. A hallmark feature of selenoproteins is the incorporation of selenium as the amino acid selenocysteine (Sec) in their primary structure. Sec is encoded by the UGA codon, recognized as a stop codon. Circumvention of the stop recognition occurs due to a combination of cis and trans factors that have been extensively reviewed elsewhere [10,11,12,13,14,15,16,17,18]
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