GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1

ABSTRACT: Age-related obesity is a growing public health concern since it contributes to a multitude of metabolic disorders, yet its mechanisms remain poorly defined. Herein, we report that S-nitrosoglutathione reductase (GSNOR), a pivotal enzyme for de-nitrosation, significantly increased in adipose tissues in both naturally middle-aged mice and human. Knocking out (KO) GSNOR in mice leads to weight reduction, diminished adipose mass and improved metabolism, while adipose tissue-specific overexpression of GSNOR (KI) results in obesity and metabolism decline. Further study showed that aged GSNOR KO mice had higher mitochondrial content and beige adipocytes, but adipose-specific GSNOR overexpression promoted adipose tissue whitening. Quantitative S-nitrosation proteomic analysis indicate S-nitrosation of Beclin-1 at cysteine 351 decreased significantly in aging mice and GSNOR KI mice. Beclin-1C351A mutation promoted autophagy by facilitating the interaction between Beclin-1 and ATG14, thereby accelerating the conversion of beige to white adipocytes. Notably, age-related obesity is abrogated by specific knocking down GSNOR in adipose tissue. This study reveals a new mechanism and a novel therapeutic avenue for managing age-related obesity.

ORGANISM(S): Mus <genus>

SUBMITTER: Chang Chen  

PROVIDER: PXD072412 | iProX | Thu Dec 25 00:00:00 GMT 2025

REPOSITORIES: iProX