Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
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 Tx...
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Published in | Scientific reports Vol. 6; no. 1; p. 28080 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
27.06.2016
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Cardiovascular and Metabolic Disease Translational Medicine Unit, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, SE-431 83 Mölndal, Sweden. |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/srep28080 |