Fatty acid‐induced induction of Toll‐like receptor‐4/nuclear factor‐κB pathway in adipocytes links nutritional signalling with innate immunity
Open accessAbstract
To study the effects of fatty acids and the involvement of the Toll-like receptor-4/nuclear factor-kappaB (TLR-4/NF-kappaB) pathway with respect to the secretion of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with increasing doses of fatty acids. The secretion of adiponectin, resistin and monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay. The NF-kappaB p65 nuclear translocation and TLR-4 expression were investigated by Western blot. The effects mediated by NF-kappaB were tested using a specific NF-kappaB-inhibitor and TLR-4-induced effects were analysed with a neutralizing TLR-4 antibody. Binding of (14)C-labelled fatty acids to TLR-4/MD-2 was investigated using a FLAG-tagged extracellular part of TLR-4 fused to full-length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high-fat diet was investigated by reverse transcription-polymerase chain reaction. The TLR-4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acids on MCP-1 secretion and of palmitoleic acid on resistin secretion are mediated via NF-kappaB. The stimulatory effects of stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory effect of stearic acid on MCP-1 secretion are mediated via TLR-4. Fatty acid-mediated effect…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
FFA activates NF-κB through TLR4, leading to the expression of monocyte chemotactic protein-1 to recruit macrophages, which further produce IL-6 and TNFα.
“In line with these findings, FFA activates NF-κB through TLR4, leading to the expression of monocyte chemotactic protein-1 (MCP-1) to recruit macrophages, which further produce IL-6 and TNFα (307, 308).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [308]
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · see citing works
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760 · see citing works
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690 · see citing works
Suganami, T., Nishida, J., & Ogawa, Y. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000183883.72263.13 · Cited by 1,056 · see citing works
Bajaj, M., Suraamornkul, S., Kashyap, S., Cusi, K., Mandarino, L., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0224 · Cited by 109 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“In line with these findings, FFA activates NF-κ B through TLR4, leading to the expression of monocyte chemo-tactic protein-1 (MCP-1) to recruit macrophages, which further produce IL-6 and TNF α (307, 308).”
BackgroundFetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance
Pal, D., Dasgupta, S., Kundu, R., Maitra, S., Das, G., Mukhopadhyay, S., Ray, S., Majumdar, S. S., & Bhattacharya, S. (2012) · Nature Medicine · doi:10.1038/nm.2851 · Cited by 922 · see citing works
Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity
Donath, M. Y., Dalmas, É., Sauter, N. S., & Böni-Schnetzler, M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.001 · Cited by 338 · see citing works
Innate immunity and adipose tissue biology
Schäffler, A., & Schölmerich, J. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.03.001 · Cited by 283 · see citing works
Obesity, pregnancy, inflammation, and vascular function
Denison, F. C., Roberts, K. A., Barr, S. M., & Norman, J. E. (2010) · Reproduction · doi:10.1530/rep-10-0074 · Cited by 221 · see citing works
Zhu, M. J., Ma, Y., Long, N. M., Du, M., & Ford, S. P. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00309.2010 · Cited by 137 · see citing works
Sen, Z. D., Danyeli, L. V., Woelfer, M., Lamers, F., Wagner, G., Sobanski, T., & Walter, M. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.12.020 · Cited by 65 · see citing works
Shen, X., Yang, L., Yan, S., Zheng, H., Liang, L., Cai, X., & Liao, M. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.014 · Cited by 63 · see citing works
Bilbo, S. D. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.02.017 · Cited by 46 · see citing works
Physiological and pathophysiological actions of insulin in the liver
Kubota, N., Kubota, T., & Kadowaki, T. (2025) · Endocrine Journal · doi:10.1507/endocrj.ej24-0192 · Cited by 19 · see citing works
- Authors
- Schaeffler, A., Gross, P., Buettner, R., Bollheimer, C., Buechler, C., Neumeier, M., Kopp, A., Schoelmerich, J., & Falk, W.
- Affiliations
- University Hospital Regensburg (DE)
- Corresponding author
- Falk, Werner
- ORCID
- Buechler, Christa
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2009-01-05
- Volume
- 126
- Issue
- 2
- Pages
- 233-245
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- PMC
- PMC2632685
- OpenAlex
- W1980152778
- Cited by
- 360
- References
- 5
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 20 · 2019: 19 · 2018: 22 · 2017: 22 · 2016: 20 · 2015: 26 · 2014: 28 · 2013: 30 · 2012: 28
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- TLR4, NF-κB, fatty acids, adipocytes, adipokine secretion, innate immunity, adiponectin, resistin, MCP-1, stearic acid, palmitic acid, palmitoleic acid, adipogenesis, high-fat diet, abdominal fat
- MeSH terms
- Animals, Animal Nutritional Physiological Phenomena, Cell Differentiation, Cells, Cultured, Diet, Dietary Fats, Fatty Acids, Immunity, Innate, Male, Signal Transduction, NF-kappa B, Rats, Wistar, Adipocytes, Chemokine CCL2, Reverse Transcriptase Polymerase Chain Reaction, Abdominal Fat, Toll-Like Receptor 4, Rats, Adiponectin, Resistin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review