Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice

Autor(es):Mostrar menos -

Seale, Lucia A. ^[1] ; Khadka, Vedbar S. ^[2] ; Menor, Mark ^[2] ; Xie, Guoxiang ^{[3, 4]} ; Watanabe, Ligia M. ^[1] ; Sasuclark, Alexandru ^[1] ; Guirguis, Kyrillos ^[1] ; Ha, Herena Y. ^[1] ; Hashimoto, Ann C. ^[1] ; Peplowska, Karolina ^{[5, 6]} ; Tiirikainen, Maarit ^{[5, 6]} ; Jia, Wei ^{[3, 4]} ; Berry, Marla J. ^[1] ; Deng, Youping ^[2]

Afiliação do(s) autor(es)

^[1] Univ Hawaii, John A Burns Sch Med, Dept Cell & Mol Biol, Honolulu, HI 93813 - USA

^[2] Univ Hawaii, John A Burns Sch Med, Dept Quantitat Hlth Sci, Bioinformat Core Facil, Honolulu, HI 96813 - USA

^[3] Univ Hawaii, Canc Ctr, Canc Biol Program, Honolulu, HI 96813 - USA

^[4] Univ Hawaii, Canc Ctr, Metabol Shared Resource, Honolulu, HI 96813 - USA

^[5] Univ Hawaii, Canc Ctr, Populat Sci Pacific Program, Honolulu, HI 96813 - USA

^[6] Univ Hawaii, Canc Ctr, Genom & Bioinformat Shared Resource, Honolulu, HI 96813 - USA

• Tipo de documento: Artigo Científico
• Fonte: NUTRIENTS; v. 11, n. 11 NOV 2019.
• Citações Web of Science: 0

Resumo

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly(-/-) or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways. (AU)

• Processo FAPESP: 18/09478-4 - Efeito da suplementação com selênio em camundongos com hipercolesterolemia em uso de estatinas
• Beneficiário: Lígia Moriguchi Watanabe
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado