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

Author(s)

Seale, Lucia A. ^{[1, 2]} ; Ogawa-Wong, Ashley N. ^[1] ; Watanabe, Ligia M. ^{[1, 3]} ; Khadka, Vedbar S. ^[4] ; Menor, Mark ^[4] ; Torres, Daniel J. ^{[1, 2]} ; Carlson, Bradley A. ^[5] ; Hatfield, Dolph L. ^[5] ; Berry, Marla J. ^[2]

Affiliation

^[1] Univ Hawaii Manoa, John A Burns Sch Med, Dept Cell & Mol Biol, Honolulu, HI 96813 - USA

^[2] Univ Hawaii Manoa, Sch Ocean & Earth Sci & Technol, Pacific Biomed Res Ctr, Honolulu, HI 96822 - USA

^[3] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Sao Paulo - Brazil

^[4] Univ Hawaii Manoa, John A Burns Sch Med, Dept Quantitat Hlth Sci, Honolulu, HI 96822 - USA

^[5] NCI, Mol Biol Selenium Sect, Mouse Genet Program, NIH, Bethesda, MD 20892 - USA

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 2 JAN 2021.
• Web of Science Citations: 0

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 (Trsp(f/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, Trsp(f/f)-Ucp1-Cre(+/-) mice maintain oxygen consumption and Ucp1 expression, with male Trsp(f/f)-Ucp1-Cre(+/-) mice accumulating more triglycerides in BAT than both female Trsp(f/f)-Ucp1-Cre(+/-) mice or Trsp(f/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 Trsp(f/f)-Ucp1-Cre(+/-) mice. Microarray analysis of BAT from Trsp(f/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 Trsp(f/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 Trsp(f/f)-Ucp1-Cre (+/-) mice implicate a mild thyroid hormone dysfunction in brown adipocytes. (AU)

• FAPESP's process: 18/09478-4 - Effects of selenium supplementation in mice with hypercholesterolemia using statin
• Grantee: Lígia Moriguchi Watanabe
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate