Nature Communications, 23 February, 2026, DOI：https://doi.org/10.1038/s41467-026-69793-3
S-nitrosoglutathione reductase GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1
Xinhua Qiao, Ting Xie, Yuying Zhang, Chuanxin Sun, Xuanhao Wu, Yuzhe Chen, Qin Yao, Haoyang Shi, Shilong Li, Hongyu Zhao, Tiepeng Wang, Jiao Meng, Li Zhou, Mutian Niu, Yangxi Hu, Hansong Liu & Chang Chen
Abstract
Age-related obesity is a growing public health concern linked to various metabolic disorders, yet its underlying mechanisms remain incompletely understood. Here we report that S-nitrosoglutathione reductase (GSNOR), a pivotal denitrosation enzyme, increases in adipose tissue of both male mice and humans from middle-age. GSNOR knockout protects against age-related weight gain and enhances metabolism, whereas adipose-specific GSNOR knock-in mice promotes obesity and metabolic decline. Further investigation reveals that aged GSNOR KO mice maintain higher mitochondrial content and more beige adipocytes, whereas adipose-specific GSNOR overexpression promotes adipose tissue whitening. Mechanistically, GSNOR denitrosates Beclin-1 at cysteine 351 and mutation of this site (Beclin-1C351A) increases autophagy by enhancing Beclin-1 and ATG14 interaction, thereby accelerating beige-to-white adipocyte conversion. Together, our findings reveal that GSNOR regulates adipose tissue remodeling during aging through Beclin-1 S-nitrosation, pointing to a potential therapeutic target for age-related obesity.
文章链接：https://www.nature.com/articles/s41467-026-69793-3
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