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Peng, X.* ; Giménez-Cassina, A.* ; Petrus, P.* ; Conrad, M. ; Rydén, M.* ; Arner, E.S.J.*

Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness.

Sci. Rep. 6:28080 (2016)
Publ. Version/Full Text Supplement DOI
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mitotic Clonal Expansion; Oxygen Species Mediate; Adipose-tissue; Cell-cycle; Adiponectin Production; Binding-protein; Oxidized Ptp1b; Human Obesity; Mice Lacking; Adipogenesis
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 28080 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed