ArticleProceedings of the National Academy of Sciences of the United States of America2009
Signaling mechanisms involved in altered function of macrophages from diet-induced obese mice affect immune responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Host insulin resistance caused byFrontiers in cellular and infection microbiology · 2023Pooled it
- Change of periodontal inflammatory indicators through a 4-week weight control intervention including caloric restriction and exercise training in young Koreans: a pilot study.BMC oral health · 2015Trial
- CTMP-REV7 axis modulates MHC-I antigen presentation via CDK1-AKT crosstalk in MSI-L/MSS colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Obesity prolongs the pro-inflammatory response and attenuates bone healing on titanium implants.Acta biomaterialia · 2025Article
- Unraveling the Complex Nexus of Macrophage Metabolism, Periodontitis, and Associated Comorbidities.Journal of innate immunity · 2025Review
- Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review).Molecular medicine reports · 2024Review
- PRAME promotes proliferation of multiple myeloma cells through CTMP/Akt/p21/CCND3 axis by ubiquitinating CTMP and p21.Heliyon · 2024Article
- The Effect of Vit-D Supplementation on the Side Effect of BioNTech, Pfizer Vaccination and Immunoglobulin G Response Against SARS-CoV-2 in the Individuals Tested Positive for COVID-19: A Randomized Control Trial.Clinical nutrition research · 2023Article
- Obesity, Bone Loss, and Periodontitis: The Interlink.Biomolecules · 2022Review
- Review
- Aberrant Periodontal and Systemic Immune Response of Overweight Rodents to Periodontal Infection.BioMed research international · 2019Article
- ExacerbatedJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Chemerin and PEDF Are Metaflammation-Related Biomarkers of Disease Activity and Obesity in Rheumatoid Arthritis.Frontiers in medicine · 2018Article
- CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-Mediators of inflammation · 2018Article
- Adaptive Upregulation of Clumping Factor A (ClfA) by Staphylococcus aureus in the Obese, Type 2 Diabetic Host Mediates Increased Virulence.Infection and immunity · 2017Article
- Caloric Restriction and Formalin-Induced Inflammation: An Experimental Study in Rat Model.Iranian Red Crescent medical journal · 2015Article
- A humoral immune defect distinguishes the response to Staphylococcus aureus infections in mice with obesity and type 2 diabetes from that in mice with type 1 diabetes.Infection and immunity · 2015Article
- Diet-induced obesity attenuates endotoxin-induced cognitive deficits.Physiology & behavior · 2015Article
- Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.The Journal of biological chemistry · 2015Article
- Phosphorylation of glycogen synthase kinase-3β in metabolically abnormal obesity affects immune stimulation-induced cytokine production.International journal of obesity (2005) · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent research links diet-induced obesity (DIO) with impaired immunity, although the underlying mechanisms remain unclear. We find that the induction of inducible NO synthase (iNOS) and cytokines is suppressed in mice with DIO and in bone marrow macrophages (BMMPhi) from mice with DIO exposed to an oral pathogen, Porphyromonas gingivalis. BMMPhi from lean mice pre-treated with free fatty acids (FFAs) and exposed to P. gingivalis also exhibit a diminished induction of iNOS and cytokines. BMMPhi from lean and obese mice exposed to P. gingivalis and analyzed by a phosphorylation protein array show a reduction of Akt only in BMMPhi from mice with DIO. This reduction is responsible for diminished NF-kappaB activation and diminished induction of iNOS and cytokines. We next observed that Toll-like receptor 2 (TLR2) is suppressed in BMMPhi from DIO mice whereas carboxy-terminal modulator protein (CTMP), a known suppressor of Akt phosphorylation, is elevated. This elevation stems from defective TLR2 signaling. In BMMPhi from lean mice, both FFAs and TNF-alpha--via separate pathways--induce an increase in CMTP. However, in BMMPhi from DIO mice, TLR2 can no longer inhibit the TNF-alpha-induced increase in CTMP caused by P. gingivalis challenge. This defect can then be restored by transfecting WT TLR2 into BMMPhi from DIO mice. Thus, feeding mice a high-fat diet over time elevates the CTMP intracellular pool, initially via FFAs activating TLR2 and later when the defective TLR2 is unable to inhibit TNF-alpha-induced CTMP. These findings unveil a link between obesity and innate immunity.
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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.