A groundbreaking study published in the journal Engineering has unveiled a crucial role for fucosylated immunoglobulin G (IgG) in driving adipose tissue dysfunction during aging. This discovery sheds new light on the molecular underpinnings of metabolic decline with age and suggests that targeting IgG fucosylation could pave the way for innovative therapies aimed at combating age-associated metabolic disorders. The research, conducted collaboratively by scientists from North China University of Science and Technology and Capital Medical University, offers unprecedented insights into how post-translational modifications of immune molecules influence adipose tissue health.
At the heart of the investigation lies a comprehensive multi-omics approach integrating transcriptomic and glycoproteomic analyses of epididymal white adipose tissue (eWAT) harvested from both young and aged murine models. Through RNA sequencing, the researchers detected a marked downregulation of key adipogenic genes in aged tissue, an observation consistent with diminished capacity for fat cell differentiation and metabolic function. Concurrently, genes linked to inflammation and fibrosis were significantly upregulated, outlining a clear molecular signature of adipose tissue deterioration driven by aging processes.
Going beyond transcriptomics, the study employed state-of-the-art N- and O-glycoproteomic profiling which illuminated widespread alterations in protein glycosylation patterns in the aged eWAT microenvironment. Notably, glycoproteins showing differential glycosylation were predominantly localized to the extracellular matrix and extracellular space, implicating these modifications in modulating cell–matrix interactions, immune signaling pathways, and the innate immune response. These findings underscore the complexity of aging-related systemic changes, highlighting glycosylation as a dynamic modulator of tissue physiology.
Among the glycosylation changes, N-fucosylation of IgG subclasses (IgG1, IgG2a, and IgG3) was significantly elevated in aged adipose tissue, while only IgG2a exhibited increased O-fucosylation. This selective enhancement of fucosylation points to a subtype-specific regulation of IgG glycans during aging, with functional implications. The aberrant fucosylation of IgG molecules not only serves as a molecular hallmark of aging but may actively contribute to the dysregulated inflammatory milieu observed in senescent adipose tissue.
To causally interrogate the role of fucosylated IgG in vivo, the researchers developed a sophisticated animal model involving B-cell depletion in aged mice to reduce endogenous IgG levels. This manipulation led to a restoration of adipogenic gene expression and a suppression of fibrotic markers, indicating that IgG plays a direct role in mediating tissue remodeling and metabolic balance. Crucially, reconstitution experiments with either fucosylated or nonfucosylated IgG revealed stark differences; fucosylated IgG exacerbated inflammation and fibrosis while more profoundly inhibiting the adipogenic program compared to its nonfucosylated counterpart.
The evidence collectively points to fucosylated IgG as a pathogenic driver of age-associated adipose tissue dysfunction, operating through mechanisms that enhance chronic inflammation and tissue fibrosis while impairing fat cell regeneration. These effects likely contribute to systemic metabolic decline, insulin resistance, and the progression of age-related diseases such as type 2 diabetes and cardiovascular disorders. The molecular details highlighted in this study open new avenues for interventions that could selectively target IgG glycosylation profiles to mitigate metabolic aging.
Intriguingly, this research places the immune system’s adaptive arm—and specifically the post-translational modification of antibodies—at the nexus of metabolic regulation in aging. It expands the paradigm beyond classical immunosenescence by demonstrating how glycan remodeling on IgG alters tissue homeostasis and inflammatory set points. This conceptual advance underscores the importance of glycoimmunology in understanding complex age-related pathologies and devising novel therapeutic strategies.
From a translational perspective, modulating IgG fucosylation could become a promising strategy to rejuvenate aging adipose tissue function and thus improve metabolic healthspan. Potential approaches may include the development of small molecule inhibitors targeting fucosyltransferases, glycoengineering of therapeutic antibodies, or immune-modulating therapies that recalibrate IgG glycosylation patterns. Furthermore, circulating fucosylated IgG levels might serve as valuable biomarkers to monitor adipose dysfunction and metabolic risk in aging populations.
The study also highlights the broader importance of extracellular matrix remodeling and glycoprotein signaling networks in adipose tissue aging. Alterations in glycosylation of extracellular proteins appear to coordinate inflammatory cell infiltration, fibrotic remodeling, and impaired adipogenesis. These multifaceted modifications suggest a highly orchestrated process whereby glycan changes propagate age-related tissue dysfunction, thus establishing glycosylation as both a marker and mediator of systemic aging processes.
Overall, the identification of fucosylated IgG as a critical molecular mediator connecting the immune system with metabolic decline represents a significant step forward in aging research. It challenges existing dogmas and invites a rethinking of how immune glycoproteins influence organ function over the lifespan. This innovative work paves the way for new scientific inquiries into the roles of antibody glycosylation in other age-related tissues and diseases, potentially revolutionizing the field of immunometabolism.
The full research article titled “Fucosylated IgG Contributes to Adipose Tissue Dysfunction During Aging” was authored by Jingyu Wang, Wei Su, Haotian Wang, Licui Liu, Jinlong Li, and Youxin Wang. Published on February 17, 2026, in Engineering, the paper is accessible via open access and provides comprehensive experimental details and data supporting these novel findings. Interested readers and researchers can explore the full text at: https://doi.org/10.1016/j.eng.2025.10.008.
Subject of Research: The role of fucosylated immunoglobulin G in adipose tissue dysfunction and aging-related metabolic decline.
Article Title: Fucosylated IgG Contributes to Adipose Tissue Dysfunction During Aging
News Publication Date: 17-Feb-2026
Web References:
https://doi.org/10.1016/j.eng.2025.10.008
https://www.sciencedirect.com/journal/engineering
Image Credits: Jingyu Wang, Wei Su et al.
Keywords
Aging, fucosylated IgG, adipose tissue dysfunction, glycosylation, immunoglobulin G, metabolic disorders, inflammation, fibrosis, transcriptomics, glycoproteomics, immunometabolism, B-cell depletion, extracellular matrix.
Tags: adipogenic gene regulation in agingadipose tissue dysfunction mechanismsage-associated metabolic disorders therapyfucosylated IgG in agingglycoproteomic profiling of adipose tissueimmunoglobulin G glycosylationinflammation and fibrosis in aging fatmetabolic decline in elderlymulti-omics in adipose researchmurine models of adipose agingpost-translational modification in metabolismtranscriptomic changes in aged fat
