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Kiermayer, C. ; Erdelen, R. ; Schriever, S.C. ; Böhm, R. ; Prehn, C. ; Artati, A. ; Kleinert, M.* ; Miller, M. ; Dyar, K.A. ; Schmid, R.M.* ; Pfluger, P.T. ; Adamski, J. ; Brielmeier, M.

Txnrd2 loss in skeletal muscle causes muscle atrophy and drives leanness and obesity resistance.

Redox Biol. 93:104165 (2026)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
The mitochondrial selenoenzyme thioredoxin reductase 2 (TXNRD2) plays a critical role in redox homeostasis and reactive oxygen species ( ROS) scavenging. While heart-specific deletion of Txnrd2 in mice resulted in cardiac dysfunction, TXNRD2 function in skeletal muscle, the major component of lean body mass, remains unclear. In human GWAS the TXNRD2 locus is associated with total lean mass. Here, we show that Txnrd2 muscle-specific knockout (mTKO) induces a lean phenotype characterized by muscle atrophy and diminished adipose tissues. mTKO mice were resistant to weight gain on standard and high-fat diet. Whole body glucose clearance was increased, and ATP levels in muscle were decreased, suggesting impaired mitochondrial energy production. Transcriptomic and metabolomic analyses revealed alterations in one-carbon metabolism and related pathways. Despite elevated glutathione levels, changes in key factors of cellular detoxification were consistent with compromised antioxidant defence system. In sum, we unravel that Txnrd2 deficiency in skeletal muscle rewires whole-body energy metabolism through mitochondrial dysfunction and impaired redox capacity.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2213-2317
e-ISSN 2213-2317
Journal Redox Biology
Quellenangaben Volume: 93, Issue: , Pages: , Article Number: 104165 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) CF Laboratory Animal Services (CF-LAS)
Institute of Diabetes and Obesity (IDO)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Diabetes and Cancer (IDC)
Institute of Experimental Genetics (IEG)