GSNOR drives age-related obesity by regulating the S-nitrosation of Beclin-1 to promote adipose tissue whitening

To elucidate the potential mechanisms of GSNOR in age-related obesity, we performed protein quantitative proteomics and quantitative S-nitrosation proteomics to investigate the levels and sites of protein S-nitrosation in iWATs from control and KI mice. The abundance ratios of proteins and their S-nitrosation states (KI/WT) were assessed, with ratios greater than 1.2 and less than 0.8 considered statistically significant. The results indicated that the KI group exhibited a marked reduction in S-nitrosation modification targets, with approximately half of the identified targets showing significant downregulation. A clustering analysis of differentially expressed proteins between the two groups highlighted that molecular functions related to fatty acid metabolism and cellular components associated with mitochondria were enriched. We subsequently focused on the top-ranked downregulated (≤0.8) S-nitrosation proteins that were most closely associated with fatty acid metabolism and mitochondria. Beclin-1, a core member of autophagy, attracted our attention, and we determined that cysteine 351 of Beclin-1 was S-nitrosated.