title: Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness.
abstract: Recently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txnrd1 (Txnrd1(-/-)) displayed increased metabolic flux, glycogen storage, lipogenesis and adipogenesis. This phenotype coincided with upregulated PPARγ expression, promotion of mitotic clonal expansion and downregulation of p27 and p53. Enhanced Akt activation also contributed to augmented adipogenesis and insulin sensitivity. Knockdown of TXNRD1 transcripts accelerated adipocyte differentiation also in human primary preadipocytes. Furthermore, TXNRD1 transcript levels in subcutaneous adipose tissue from 56 women were inversely associated with insulin sensitivity in vivo and lipogenesis in their isolated adipocytes. These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulation.
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Peng
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.|Departamento de Biología Molecular, Universidad Autónoma de Madrid, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), 28049, Madrid, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Giménez-Cassina
authors.affiliation: Clinical Research Center, and the Department of Medicine, Huddinge University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Petrus
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Conrad
authors.affiliation: Clinical Research Center, and the Department of Medicine, Huddinge University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Elias S J
authors.initials: ES
authors.lastname: Arnér
mesh_terms: D017667:Adipocytes / Q000201:enzymology*; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; C516125:Txnrd1 protein, mouse