Fucosylated IgG drives adipose tissue dysfunction during aging

A study published in Engineering has identified fucosylated immunoglobulin G (IgG) as a key mediator contributing to adipose tissue dysfunction during aging, offering insights into age-related metabolic disorders and potential therapeutic targets.

Researchers from North China University of Science and Technology and Capital Medical University conducted transcriptomic and glycoproteomic analyses on epididymal white adipose tissue (eWAT) from young and aged mice. RNA-sequencing results showed significant downregulation of adipogenic genes in aged eWAT, accompanied by elevated expression of inflammatory and fibrotic markers, which were validated by quantitative polymerase chain reaction. Comprehensive N- and O-glycoproteomic profiling revealed widespread glycosylation changes in aged adipose tissue, with differentially glycosylated proteins mainly located in the extracellular space and involved in innate immune responses, transport, signal transduction, and extracellular matrix-receptor interaction pathways.

Notably, IgG glycosylation levels were significantly increased in aged mice. The N-fucosylation of IgG1, IgG2a, and IgG3 was elevated, while only IgG2a showed increased O-fucosylation, indicating N-fucosylation as a common age-related modification across IgG subtypes. In vivo experiments demonstrated that B-cell depletion-induced IgG reduction enhanced adipogenic gene expression and suppressed fibrotic marker expression in aged mice. These effects were reversed by repletion with either fucosylated or nonfucosylated IgG. Compared with nonfucosylated IgG, fucosylated IgG exacerbated inflammation and fibrosis while more strongly inhibiting adipogenesis, confirming its role in driving age‑related adipose dysfunction.

The findings link IgG fucosylation to metabolic decline, chronic inflammation, and fibrosis in aging adipose tissue. Modulating IgG fucosylation may represent a potential strategy to alleviate age-related metabolic disorders and improve health in older populations.

The paper "Fucosylated IgG Contributes to Adipose Tissue Dysfunction During Aging," is authored by Jingyu Wang, Wei Su, Haotian Wang, Licui Liu, Jinlong Li, Youxin Wang.