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 <i>cis</i> and <i>trans</i> factors required during transl...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/2/611 |
| _version_ | 1797413939150061568 |
|---|---|
| author | Lucia A. Seale Ashley N. Ogawa-Wong Ligia M. Watanabe Vedbar S. Khadka Mark Menor Daniel J. Torres Bradley A. Carlson Dolph L. Hatfield Marla J. Berry |
| author_facet | Lucia A. Seale Ashley N. Ogawa-Wong Ligia M. Watanabe Vedbar S. Khadka Mark Menor Daniel J. Torres Bradley A. Carlson Dolph L. Hatfield Marla J. Berry |
| author_sort | Lucia A. Seale |
| collection | DOAJ |
| description | 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 <i>cis</i> and <i>trans</i> factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA<sup>[Ser]Sec</sup>, encoded in mice by the gene <i>Trsp</i>. Whole-body deletion of <i>Trsp</i> in mouse is embryonically lethal, while targeted deletion of <i>Trsp</i> 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 <i>Trsp</i> in brown adipocytes (<i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup>), 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, <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice maintain oxygen consumption and Ucp1 expression, with male <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice accumulating more triglycerides in BAT than both female <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice or <i>Trsp<sup>f/f</sup></i> 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 <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice. Microarray analysis of BAT from <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice revealed glutathione S-transferase alpha 3 (<i>Gsta3</i>) and ELMO domain containing 2 (<i>Elmod2</i>) as the transcripts most affected by the loss of <i>Trsp</i>. Male <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes <i>Thrsp</i> and <i>Tshr</i> in their BATs. In summary, modest changes in the BAT of <i>Trsp<sup>f/f</sup>-Ucp1-Cre <sup>+/−</sup></i> mice implicate a mild thyroid hormone dysfunction in brown adipocytes. |
| first_indexed | 2024-03-09T05:25:03Z |
| format | Article |
| id | doaj.art-2d43738860a5468c96dcc775e01f2507 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:25:03Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2d43738860a5468c96dcc775e01f25072023-12-03T12:36:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122261110.3390/ijms22020611Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown AdipocytesLucia A. Seale0Ashley N. Ogawa-Wong1Ligia M. Watanabe2Vedbar S. Khadka3Mark Menor4Daniel J. Torres5Bradley A. Carlson6Dolph L. Hatfield7Marla J. Berry8Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USADepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USADepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USADepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USADepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USADepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USAMolecular Biology of Selenium Section, Mouse Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Biology of Selenium Section, Mouse Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAPacific Biomedical Research Center, School of Ocean and Earth Science and Technology, University of Hawaii at Manoa, Honolulu, HI 96822, USASelenoproteins 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 <i>cis</i> and <i>trans</i> factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA<sup>[Ser]Sec</sup>, encoded in mice by the gene <i>Trsp</i>. Whole-body deletion of <i>Trsp</i> in mouse is embryonically lethal, while targeted deletion of <i>Trsp</i> 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 <i>Trsp</i> in brown adipocytes (<i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup>), 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, <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice maintain oxygen consumption and Ucp1 expression, with male <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice accumulating more triglycerides in BAT than both female <i>Trsp<sup>f/f</sup>-Ucp1-Cre</i><sup>+/−</sup> mice or <i>Trsp<sup>f/f</sup></i> 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 <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice. Microarray analysis of BAT from <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice revealed glutathione S-transferase alpha 3 (<i>Gsta3</i>) and ELMO domain containing 2 (<i>Elmod2</i>) as the transcripts most affected by the loss of <i>Trsp</i>. Male <i>Trsp<sup>f/f</sup>-Ucp1-Cre<sup>+/−</sup></i> mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes <i>Thrsp</i> and <i>Tshr</i> in their BATs. In summary, modest changes in the BAT of <i>Trsp<sup>f/f</sup>-Ucp1-Cre <sup>+/−</sup></i> mice implicate a mild thyroid hormone dysfunction in brown adipocytes.https://www.mdpi.com/1422-0067/22/2/611Sec-tRNA<sup>[Ser]Sec</sup>selenoproteinsbrown adipose tissue |
| spellingShingle | Lucia A. Seale Ashley N. Ogawa-Wong Ligia M. Watanabe Vedbar S. Khadka Mark Menor Daniel J. Torres Bradley A. Carlson Dolph L. Hatfield Marla J. Berry Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes International Journal of Molecular Sciences Sec-tRNA<sup>[Ser]Sec</sup> selenoproteins brown adipose tissue |
| title | Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes |
| title_full | Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes |
| title_fullStr | Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes |
| title_full_unstemmed | Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes |
| title_short | Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes |
| title_sort | adaptive thermogenesis in a mouse model lacking selenoprotein biosynthesis in brown adipocytes |
| topic | Sec-tRNA<sup>[Ser]Sec</sup> selenoproteins brown adipose tissue |
| url | https://www.mdpi.com/1422-0067/22/2/611 |
| work_keys_str_mv | AT luciaaseale adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT ashleynogawawong adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT ligiamwatanabe adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT vedbarskhadka adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT markmenor adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT danieljtorres adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT bradleyacarlson adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT dolphlhatfield adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes AT marlajberry adaptivethermogenesisinamousemodellackingselenoproteinbiosynthesisinbrownadipocytes |