REVIEW article
Front. Immunol.
Sec. B Cell Biology
Temporal dynamics of IgG-mediated immunometabolic dysfunction: From acute obesity to chronic aging
Provisionally accepted
- 1College of Medicine, Kyung Hee University, Dongdaemun-gu, Republic of Korea
- 2Kyung Hee University Hospital at Gangdong, Gangdong-gu, Republic of Korea
- 3Hankuk University of Foreign Studies, Dongdaemun-gu, Republic of Korea
- 4Kyung Hee University College of Medicine, Dongdaemun-gu, Republic of Korea
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Immunoglobulin G (IgG) is traditionally recognized as a circulating immune effector; however, recent discoveries have revealed that IgG accumulates in adipose tissue—up to 16-fold above plasma levels—and functions as a critical mediator of metabolic dysfunction in obesity and aging. This review summarizes evidence showing that adipocyte IgG accumulation occurs via neonatal Fc receptor (FcRn)-mediated uptake and directly competes with insulin for receptor binding through Fc-CH3 domain interactions. IgG initiates tissue-specific inflammatory responses. Functional outcomes depend on glycosylation patterns: sialylated IgG (e.g., control IgG) signals anti-inflammatory pathways via DC-SIGN and CD22, whereas hyposialylated IgG (e.g., disease-associated IgG) activates endothelial FcγRIIB receptors, impairs insulin transcytosis, and promotes vascular insulin resistance. This mechanism may help explain the limited success of conventional anti-inflammatory treatments for metabolic diseases. The timeline of IgG-mediated effects progresses through acute inflammation (weeks), subacute deposition and insulin interference (months), and chronic fibrosis (years). Notably, FcRn antagonists can reverse insulin resistance, while restoration of IgG sialylation using sialic acid precursors improves function without depleting antibodies. These findings suggest that IgG dysfunction occurs at the intersection of obesity, aging, and metabolic disease, offering new biomarkers and therapeutic targets. Glycosylation profiling enables the discrimination between insulin-sensitive and -resistant individuals with similar body mass indices, supporting precision medicine approaches. This paradigm shift, from cell-centric to antibody-mediated models, reframes our understanding of metabolic disease pathogenesis and offers novel treatment strategies.
Keywords: IgG, FcRn, metabolic dysfunction, Insulin Resistance, adipose tissue inflammation, Immunometabolism
Received: 21 Jul 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 Kim, Kim and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Man S Kim, manskim@khu.ac.kr
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