Ligia M Watanabe1, Ann C Hashimoto2, Daniel J Torres2, Marla J Berry2, Lucia A Seale3. 1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, 96813, USA; Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo - FMRP/USP, Brazil. 2. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, 96813, USA. 3. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, 96813, USA. Electronic address: lseale@hawaii.edu.
Abstract
BACKGROUND: The amino acid selenocysteine (Sec) is an integral part of selenoproteins, a class of proteins mostly involved in strong redox reactions. The enzyme Sec lyase (SCLY) decomposes Sec into selenide allowing for the recycling of the selenium (Se) atom via the selenoprotein synthesis machinery. We previously demonstrated that disruption of the Scly gene (Scly KO) in mice leads to the development of obesity and metabolic syndrome, with effects on glucose homeostasis, worsened by Se deficiency or a high-fat diet, and exacerbated in male mice. Our objective was to determine whether Se supplementation could ameliorate obesity and restore glucose homeostasis in the Scly KO mice. METHODS: Three-weeks old male and female Scly KO mice were fed in separate experiments a diet containing 45 % kcal fat and either sodium selenite or a mixture of sodium selenite and selenomethionine (selenite/SeMet) at moderate (0.25 ppm) or high (0.5-1 ppm) levels for 9 weeks, and assessed for metabolic parameters, oxidative stress and expression of selenoproteins. RESULTS: Se supplementation was unable to prevent obesity and elevated epididymal white adipose tissue weights in male Scly KO mice. Serum glutathione peroxidase activity in Scly KO mice was unchanged regardless of sex or dietary Se intake; however, supplementation with a mixture of selenite/SeMet improved oxidative stress biomarkers in the male Scly KO mice. CONCLUSION: These results unveil sex- and selenocompound-specific regulation of energy metabolism after the loss of Scly, pointing to a role of this enzyme in the control of whole-body energy metabolism regardless of Se levels.
BACKGROUND: The amino acid selenocysteine (Sec) is an integral part of selenoproteins, a class of proteins mostly involved in strong redox reactions. The enzyme Sec lyase (SCLY) decomposes Sec into selenide allowing for the recycling of the selenium (Se) atom via the selenoprotein synthesis machinery. We previously demonstrated that disruption of the Scly gene (Scly KO) in mice leads to the development of obesity and metabolic syndrome, with effects on glucose homeostasis, worsened by Se deficiency or a high-fat diet, and exacerbated in male mice. Our objective was to determine whether Se supplementation could ameliorate obesity and restore glucose homeostasis in the Scly KO mice. METHODS: Three-weeks old male and female Scly KO mice were fed in separate experiments a diet containing 45 % kcal fat and either sodium selenite or a mixture of sodium selenite and selenomethionine (selenite/SeMet) at moderate (0.25 ppm) or high (0.5-1 ppm) levels for 9 weeks, and assessed for metabolic parameters, oxidative stress and expression of selenoproteins. RESULTS:Se supplementation was unable to prevent obesity and elevated epididymal white adipose tissue weights in male Scly KO mice. Serum glutathione peroxidase activity in Scly KO mice was unchanged regardless of sex or dietary Se intake; however, supplementation with a mixture of selenite/SeMet improved oxidative stress biomarkers in the male Scly KO mice. CONCLUSION: These results unveil sex- and selenocompound-specific regulation of energy metabolism after the loss of Scly, pointing to a role of this enzyme in the control of whole-body energy metabolism regardless of Se levels.
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Authors: John T Pinto; Boris F Krasnikov; Steven Alcutt; Melanie E Jones; Thambi Dorai; Maria T Villar; Antonio Artigues; Jianyong Li; Arthur J L Cooper Journal: J Biol Chem Date: 2014-09-17 Impact factor: 5.157
Authors: Lucia A Seale; Ann C Hashimoto; Suguru Kurokawa; Christy L Gilman; Ali Seyedali; Frederick P Bellinger; Arjun V Raman; Marla J Berry Journal: Mol Cell Biol Date: 2012-08-13 Impact factor: 4.272
Authors: Ligia M Watanabe; Ann C Hashimoto; Daniel J Torres; Naghum Alfulaij; Rafael Peres; Razvan Sultana; Alika K Maunakea; Marla J Berry; Lucia A Seale Journal: Mol Cell Endocrinol Date: 2021-05-27 Impact factor: 4.369