ArticleThe Journal of clinical investigation2018
Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States.International journal of molecular sciences · 2020Pooled it
- Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019Pooled it
- Large glycomics datasets as a tool to understand the function of glycans.Nature chemical biology · 2026Review
- B cell mechanisms underlie IgG glycan alterations in obesity.Glycobiology · 2026Article
- Immunoglobulin G in aging and cancer.Frontiers in immunology · 2026Review
- ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria.Cell reports · 2025Article
- IgG N-Glycan Profiles in Mothers and Infants Postpartum in the Context of Maternal Obesity and Gestational Diabetes.International journal of molecular sciences · 2025Article
- The Emerging Role of Sialic Acids in Obesity and Diabetes: Molecular Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- IgG N-glycosylation contributes to different severities of insulin resistance: implications for 3P medical approaches.The EPMA journal · 2025Article
- Plasma N-Glycoproteomics in monozygotic twin pairs discordant for body mass index reveals an obesity signature related to inflammation and iron metabolism.Biology direct · 2025Article
- FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.Cell metabolism · 2025Article
- Potential Glycobiomarkers in Maternal Obesity and Gestational Diabetes During Human Pregnancy.Journal of clinical medicine · 2025Article
- The Interplay Between Immunity, Inflammation and Endothelial Dysfunction.International journal of molecular sciences · 2025Review
- Temporal dynamics of IgG-mediated immunometabolic dysfunction: from acute obesity to chronic aging.Frontiers in immunology · 2025Review
- The role of autoantibodies in bridging obesity, aging, and immunosenescence.Immunity & ageing : I & A · 2024Review
- Immunoglobulin G glycosylation and its alterations in aging-related diseases.Acta biochimica et biophysica Sinica · 2024Review
- Antigen specificity shapes antibody functions in tuberculosis.bioRxiv : the preprint server for biology · 2024Article
- The role of glycans in personalization of preventive health care.Croatian medical journal · 2024Article
- Leptin receptor deficiency impedes metabolic surgery related-weight loss through inhibition of energy expenditure in db/db mice.Diabetology & metabolic syndrome · 2024Article
- New Player in an Old Field? Ecto-FArteriosclerosis, thrombosis, and vascular biology · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we have shown that activation of the IgG receptor FcγRIIB in endothelium by hyposialylated IgG plays an important role in obesity-induced insulin resistance. Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or selectively in endothelium were protected from insulin resistance as a result of the preservation of insulin delivery to skeletal muscle and resulting maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin resistance. Moreover, IgG transferred from patients with T2DM but not from metabolically healthy subjects caused insulin resistance in IgG-deficient mice via FcγRIIB, indicating that similar processes may be operative in T2DM in humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice impaired endothelial cell insulin transcytosis in culture and in vivo. These effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. Thus, IgG sialylation and endothelial FcγRIIB may represent promising therapeutic targets to sever the link between obesity and T2DM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.