The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
TLR4 links innate immunity and fatty acid-induced insulin resistance
Open accessAbstract
TLR4 is the receptor for LPS and plays a critical role in innate immunity. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of obese animals and humans and play an important role in obesity-associated insulin resistance. Here we show that nutritional fatty acids, whose circulating levels are often increased in obesity, activate TLR4 signaling in adipocytes and macrophages and that the capacity of fatty acids to induce inflammatory signaling in adipose cells or tissue and macrophages is blunted in the absence of TLR4. Moreover, mice lacking TLR4 are substantially protected from the ability of systemic lipid infusion to (a) suppress insulin signaling in muscle and (b) reduce insulin-mediated changes in systemic glucose metabolism. Finally, female C57BL/6 mice lacking TLR4 have increased obesity but are partially protected against high fat diet-induced insulin resistance, possibly due to reduced inflammatory gene expression in liver and fat. Taken together, these data suggest that TLR4 is a molecular link among nutrition, lipids, and inflammation and that the innate immune system participates in the regulation of energy balance and insulin resistance in response to changes in the nutritional environment.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Shi et al. showed that FFA activates TLR4 signaling and that mice lacking TLR4 are partially protected against high fat diet-induced insulin resistance (306).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [306]
Experimental — accuracy not yet measuredIn the citing paper
“For instance, activation of TLR4 via LPS leads to the release of pro-inflammatory cytokines (e.g., TNF, interleukin [IL]-6), but similar effects are also observed if free fatty acids bind to TLR4.63”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [63]
In the citing paper
“A number of free fatty acid products released from necrotic adipocytes have been shown to cause pro-inflammatory activation of macrophages through TLR-2 and TLR-4 signaling pathways, suggesting a potential mechanism by which obesity-induced inflammation may occur [73,74].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [74]
In the citing paper
“A number of studies have shown that TLR-4 deficient mice are not protected from diet-induced obesity, but are protected from obesity-induced insulin resistance [74,76,77].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [74]
In the citing paper
“Probiotics intake may improve markers of insulin metabolism and lipid profiles by reducing cytokines and suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (Shi et al., 2006) and gut microbiota-short chain fatty acids (SCFA)-hormone axis (Yadav et al., 2013).”
From Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial (2016) · cites this paper as Shi et al., 2006
In the citing paper
“Weight loss induced by gastric bypass reduced the circulating concentrations of visfatin (123) and TNF-a (124,125) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [125]
In the citing paper
“An important component of these fatty acid-induced activation events are the pattern recognition receptors TLR2 and TLR4 (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [116]
In the citing paper
“In line with this, Tlr4-KO mice are protected against lipid-and obesity-induced insulin resistance (116, 117).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [116]
In the citing paper
“Clearly, ATMs exist in a lipid-rich environment and fatty acids can broadly activate the macrophage inflammatory program (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [116]
In the citing paper
“Activation of inflammation is prevented in macrophages and adipocytes that are deficient in Tlr2, Tlr4, or Tlr2/Tlr4 (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [116]
In the citing paper
“Dietary-derived saturated fatty acids [26] and erythrocyte content of saturated fatty acids (indicator of long-term consumption) [27], positively correlate with circulating measures of CRP and can contribute to inflammation by favoring TLR4 signaling in macrophages [67].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [67]
In the citing paper
“However, FFAs can also serve as ligands for the TLR4 complex (33), thereby activating the classical inflammatory response in the context of increased local extracellular lipid concentrations, which ultimately drives ATMΦ accumulation (34,35).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [33]
In the citing paper
“Even though we do not consider AT as a conventional tissue suffering from lipotoxic side effects, either high rates of lipolysis or an influx of saturated FFAs into adipocytes do cause temporary inflammation within the tissue (33).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [33]
In the citing paper
“TLR4, specifically, has been shown to mediate inflammatory responses to free fatty acids, which are elevated in obesity and are associated with insulin resistance38.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
The hormone resistin links obesity to diabetes
Steppan, C. M., Bailey, S. T., Bhat, S., Brown, E. J., Banerjee, R. R., Wright, C. M., Patel, H. R., Ahima, R. S., & Lazar, M. A. (2001) · Nature · doi:10.1038/35053000 · Cited by 4,755
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3749 · Cited by 3,374
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- 10.1172/JCI200525102 · DOI · Paper page
Cited by
Sorted by citations
Items 201–300 of 1,030
Yang, Z., Kahn, B. B., Shi, H., & Xue, B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.123620 · Cited by 417
Self-citationCeramide is a cardiotoxin in lipotoxic cardiomyopathy
Park, T., Hu, Y., Noh, H. L., Drosatos, K., Okajima, K., Buchanan, J., Tuinei, J., Homma, S., Jiang, X.-C., Abel, E. D., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800147-jlr200 · Cited by 425
Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus
Akash, M. S. H., Rehman, K., & Chen, S. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24402 · Cited by 416
ER stress induces NLRP3 inflammasome activation and hepatocyte death
Lebeaupin, C., Proïcs, E., de Bieville, C.-H. D., Rousseau, D., Bonnafous, S., Patouraux, S., Adam, G., Lavallard, V., Rovère, C., Thuc, O. L., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.248 · Cited by 413
Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal
Alkhouri, N., Dixon, L. J., & Feldstein, A. E. (2009) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.09.32 · Cited by 413
NASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications
Farrell, G. C., Rooyen, D. M. V., Gan, L. T., & Chitturi, S. (2012) · Gut and Liver · doi:10.5009/gnl.2012.6.2.149 · Cited by 408
Fast food fever: reviewing the impacts of the Western diet on immunity
Myles, I. A. (2014) · Nutrition Journal · doi:10.1186/1475-2891-13-61 · Cited by 409
Nutrition, immune function and health of dairy cattle
Ingvartsen, K. L., & Moyes, K. M. (2012) · animal · doi:10.1017/s175173111200170x · Cited by 389
Metabolic factors affecting the inflammatory response of periparturient dairy cows
Sordillo, L. M., Contreras, G. A., & Aitken, S. L. (2009) · Animal Health Research Reviews · doi:10.1017/s1466252309990016 · Cited by 386
Toll-Like Receptor 4 Promotes Tubular Inflammation in Diabetic Nephropathy
Lin, M. Y., Yiu, W. H., Wu, H., Chan, L. Y. Y., Leung, J. C. K., Au, W. S., Chan, K. W., Lai, K. N., & Tang, S. C. W. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010111210 · Cited by 387
Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis
Anderson, N., & Borlak, J. T. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.00001 · Cited by 395
Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer
Cani, P. D., & Jordan, B. F. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0025-6 · Cited by 383
AMPK inhibition in health and disease
Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., & Andreelli, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488215 · Cited by 383
Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects
Reyna, S. M., Ghosh, S., Tantiwong, P., Meka, C. S. R., Eagan, P. A., Jenkinson, C. P., Cersósimo, E., DeFronzo, R. A., Coletta, D. K., Sriwijitkamol, A., et al. (2008) · Diabetes · doi:10.2337/db08-0038 · Cited by 390
Kanmani, S., & Koo, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207551 · Cited by 392
Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation
Peverill, W., Powell, L. W., & Skoien, R. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058591 · Cited by 387
Adipose Tissue and Atherosclerosis
Fantuzzi, G., & Mazzone, T. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.106.131755 · Cited by 383
Tanaka, S., Hikita, H., Tatsumi, T., Sakamori, R., Nozaki, Y., Sakane, S., Shiode, Y., Nakabori, T., Saito, Y., Hiramatsu, N., et al. (2016) · Hepatology · doi:10.1002/hep.28820 · Cited by 376
Shah, Z., Kampfrath, T., Deiuliis, J. A., Zhong, J., Pineda, C. A., Ying, Z., Xu, X., Lü, B., Moffatt, S. D., Durairaj, R., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.041418 · Cited by 378
Devaraj, S., Dasu, M. R. K., Rockwood, J., Winter, W. E., Griffen, S. C., & Jialal, I. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2185 · Cited by 374
Hariharan, R., Odjidja, E. N., Scott, D. S., Shivappa, N., Hébert, J. R., Hodge, A. M., & de Courten, B. V. (2021) · Obesity Reviews · doi:10.1111/obr.13349 · Cited by 387
Xu, X., Poulsen, K. L., Wu, L., Liu, S., Miyata, T., Song, Q., Wei, Q., Zhao, C., Lin, C., & Yang, J. B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01119-3 · Cited by 387
Impaired Preadipocyte Differentiation in Human Abdominal Obesity
Isakson, P., Hammarstedt, A., Gustafson, B., & Smith, U. (2009) · Diabetes · doi:10.2337/db08-1770 · Cited by 369
The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases
Soares, J., Pimentel‐Nunes, P., Roncon‐Albuquerque, R., & Leite-Moreira, A. F. (2010) · Hepatology International · doi:10.1007/s12072-010-9219-x · Cited by 378
Luoto, R., Laitinen, K., Nermes, M., & Isolauri, E. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114509993898 · Cited by 370
Macrophage polarization and meta-inflammation
Li, C., Xu, M. M., Wang, K., Adler, A. J., Vella, A. T., & Zhou, B. (2017) · Translational research · doi:10.1016/j.trsl.2017.10.004 · Cited by 376
The Development of Porcine Models of Obesity and the Metabolic Syndrome ,
Spurlock, M. E., & Gabler, N. K. (2008) · Journal of Nutrition · doi:10.1093/jn/138.2.397 · Cited by 370
Obesity, Inflammation, and Insulin Resistance – A Mini-Review
Zeyda, M., & Stulnig, T. M. (2009) · Gerontology · doi:10.1159/000212758 · Cited by 373
Schaeffler, A., Gross, P., Buettner, R., Bollheimer, C., Buechler, C., Neumeier, M., Kopp, A., Schoelmerich, J., & Falk, W. (2009) · Immunology · doi:10.1111/j.1365-2567.2008.02892.x · Cited by 360
Probiotics in prevention and treatment of obesity: a critical view
Kobyliak, N. M., Conte, C., Cammarota, G., Haley, A. P., Štyriak, I., Gašpar, Ľ., Fusek, J., Rodrigo, L., & Kružliak, P. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0067-0 · Cited by 373
Islet inflammation in type 2 diabetes and physiology
Eguchi, K., & Nagai, R. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88877 · Cited by 374
Inflammation as a Link between Obesity and Metabolic Syndrome
Faloia, E., Grazia, M., Robertis, M. D., Luconi, M. P., Furlani, G., & Boscaro, M. (2012) · Journal of Nutrition and Metabolism · doi:10.1155/2012/476380 · Cited by 378
Ceramides in Metabolism: Key Lipotoxic Players
Chaurasia, B., & Summers, S. A. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-031620-093815 · Cited by 365
Obesity and Cancer: The Oil that Feeds the Flame
Font-Burgada, J., Sun, B., & Karin, M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.015 · Cited by 364
Poggi, M., Bastelica, D., Gual, P., Iglesias, M. A., Grémeaux, T., Knauf, C., Peiretti, F., Verdier, M., Juhan-Vague, I., Tanti, J., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0654-8 · Cited by 361
Zhu, X., Lee, J., Timmins, J. M., Brown, J. M., Boudyguina, E. Y., Mulya, A., Gebre, A. K., Willingham, M. C., Hiltbold, E. M., Mishra, N., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801408200 · Cited by 356
The gut microbiome as therapeutic target
Cani, P. D., & Delzenne, N. M. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.012 · Cited by 365
The “Big Bang” in obese fat: events initiating obesity-induced adipose tissue inflammation
Wensveen, F. M., Valentić, S., Šestan, M., Turk Wensveen, T., & Polić, B. (2015) · European Journal of Immunology · doi:10.1002/eji.201545502 · Cited by 348
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347
Böni‐Schnetzler, M., Boller, S., Debray, S., Bouzakri, K., Meier, D. T., Prazak, R., Kerr-Conte, J. A., Pattou, F. N., Ehses, J. A., Schuit, F. C., et al. (2009) · Endocrinology · doi:10.1210/en.2009-0543 · Cited by 363
Adipose tissue-resident immune cells: key players in immunometabolism
Schipper, H. S., Prakken, B., Kalkhoven, E., & Boes, M. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.05.011 · Cited by 342
Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer
Howe, L. R., Subbaramaiah, K., Hudis, C. A., & Dannenberg, A. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2603 · Cited by 347
Chronic tissue inflammation and metabolic diseasePreprint
Lee, Y. S., & Olefsky, J. M. (2021) · Genes & Development · doi:10.1101/gad.346312.120 · Cited by 356
High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22
Gulhane, M., Murray, L., Lourie, R., Tong, H., Sheng, Y., Wang, R., Kang, A. Y. H., Schreiber, V., Wong, K. Y., Magor, G. W., et al. (2016) · Scientific Reports · doi:10.1038/srep28990 · Cited by 355
Pathophysiology of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis
Manne, V., Handa, P., & Kowdley, K. V. (2017) · Clinics in Liver Disease · doi:10.1016/j.cld.2017.08.007 · Cited by 347
Saturated long‐chain fatty acids activate inflammatory signaling in astrocytes
Gupta, S., Knight, A. G., Gupta, S., Keller, J. N., & Bruce‐Keller, A. J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07660.x · Cited by 353
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
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
Funcke, J., & Scherer, P. E. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r094060 · Cited by 357
Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat
Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E. (2008) · Obesity · doi:10.1038/oby.2008.210 · Cited by 334
Kim, S., Jin, Y., Choi, Y., & Park, T. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.03.012 · Cited by 341
Zhu, X., Owen, J. S., Wilson, M. D., Li, H., Griffiths, G. L., Thomas, M. J., Hiltbold, E. M., Fessler, M. B., & Parks, J. S. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m006486 · Cited by 331
Central effects of estradiol in the regulation of food intake, body weight, and adiposity
Brown, L. M., & Clegg, D. J. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.005 · Cited by 331
Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?
Asrih, M., & Jornayvaz, F. R. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.02.018 · Cited by 336
Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic?
Catalano, P. M., & Mouzon, S. H. (2011) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2010.11.039 · Cited by 341
Inflammation and the Metabolic Syndrome: The Tissue-Specific Functions of NF-κB
Catrysse, L., & van Loo, G. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.01.006 · Cited by 329
How gut microbes talk to organs: The role of endocrine and nervous routes
Cani, P. D., & Knauf, C. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.05.011 · Cited by 342
Lumeng, C. N., Liu, J., Geletka, L., Delaney, C., Delproposto, J., Desai, A., Oatmen, K., Martinez-Santibanez, G., Julius, A., Garg, S., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102188 · Cited by 328
Acylcarnitines activate proinflammatory signaling pathways
Rutkowsky, J. M., Knotts, T. A., Ono‐Moore, K. D., McCoin, C. S., Huang, S., Schneider, D. A., Singh, S., Adams, S. H., & Hwang, D. H. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00656.2013 · Cited by 333
Toll-like receptors: linking inflammation to metabolism
Könner, A. C., & Brüning, J. C. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.007 · Cited by 338
Islet Inflammation Impairs the Pancreatic β-Cell in Type 2 Diabetes
Donath, M. Y., Böni‐Schnetzler, M., Ellingsgaard, H., & Ehses, J. A. (2009) · Physiology · doi:10.1152/physiol.00032.2009 · Cited by 339
Chronic Exposure to a TLR Ligand Injures Hematopoietic Stem Cells
Esplin, B. L., Shimazu, T., Welner, R. S., Garrett, K. P., Nie, L., Zhang, Q., Humphrey, M. B., Yang, Q., Borghesi, L., & Kincade, P. W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003438 · Cited by 336
Gäbele, E., Dostert, K., Hofmann, C., Wiest, R., Schölmerich, J., Hellerbrand, C., & Obermeier, F. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.02.035 · Cited by 324
Goossens, G. H., Bizzarri, A., Venteclef, N., Essers, Y., Cleutjens, J. P., Konings, E., Jocken, J. W. E., Čajlaković, M., Ribitsch, V., Clément, K., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.027813 · Cited by 324
Myeloid Deletion of SIRT1 Induces Inflammatory Signaling in Response to Environmental Stress
Schug, T. T., Xu, Q., Gao, H., Peres-da-Silva, A., Draper, D. W., Fessler, M. B., Purushotham, A., & Li, X. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00657-10 · Cited by 329
Tzanavari, T., Giannogonas, P., & Karalis, K. P. (2010) · Current directions in autoimmunity · doi:10.1159/000289203 · Cited by 333
An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH
Tacke, F., Puengel, T., Loomba, R., & Friedman, S. L. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.038 · Cited by 321
Vallianou, N. G., Stratigou, T., Christodoulatos, G. S., & Dalamaga, Μ. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00352-2 · Cited by 325
Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue.
Yin, J., Gao, Z., He, Q., Zhou, D., Guo, Z., & Ye, J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90760.2008 · Cited by 319
Macrophage functions in lean and obese adipose tissue
Thomas, D. D., & Apovian, C. M. (2017) · Metabolism · doi:10.1016/j.metabol.2017.04.005 · Cited by 333
Kouchaki, E., Tamtaji, O. R., Salami, M., Bahmani, F., Daneshvar Kakhaki, R., Akbari, E., Tajabadi-Ebrahimi, M., Jafari, P., & Asemi, Z. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2016.08.015 · Cited by 317
RetractedChronic adipose tissue inflammation: all immune cells on the stage
Cildir, G., Akıncılar, S. C., & Tergaonkar, V. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.05.001 · Cited by 329
Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis
Guo, J., & Friedman, S. L. (2010) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-3-21 · Cited by 324
Karczewski, J., Śledzińska, E., Baturo, A., Jończyk, I., Maleszko, A., Maleszko, A., Samborski, P., Krasińska, B., & Dobrowolska, A. (2018) · European Cytokine Network · doi:10.1684/ecn.2018.0415 · Cited by 321
Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice
Carvalho, B. M., Guadagnini, D., Tsukumo, D. M. L., Schenka, A. A., Latuf-Filho, P., Vassallo, J., Dias, J. C., Kubota, L. T., Carvalheira, J. B. C., & Saad, M. J. A. (2012) · Diabetologia · doi:10.1007/s00125-012-2648-4 · Cited by 324
TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation
Velloso, L. A., Folli, F. B., & Saad, M. J. A. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1100 · Cited by 323
TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain
Kawamoto, T., Ii, M., Kitazaki, T., Iizawa, Y., & Kimura, H. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.01.026 · Cited by 311
It's Not How Fat You Are, It's What You Do with It That Counts
Virtue, S., & Vidal‐Puig, A. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060237 · Cited by 309
Laitinen, K., Poussa, T. A., Isolauri, E., & the Nutrition, A. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508111461 · Cited by 315
Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis
Vyas, D., Laput, G. P., & Vyas, A. K. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s60114 · Cited by 316
Zeyda, M., & Stulnig, T. M. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.07.003 · Cited by 316
Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
Sobczak, A. I. S., Blindauer, C. A., & Stewart, A. J. (2019) · Nutrients · doi:10.3390/nu11092022 · Cited by 314
Mechanisms of Inflammatory Responses in Obese Adipose Tissue
Sun, S., Ji, Y., Kersten, S., & Qi, L. (2012) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071811-150623 · Cited by 322
The metabolic nature of inflammatory bowel diseases
Adolph, T. E., Meyer, M., Schwärzler, J., Mayr, L., Grabherr, F., & Tilg, H. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00658-y · Cited by 316
Boon, J., Hoy, A. J., Stark, R., Brown, R. D., Meex, R. C. R., Henstridge, D. C., Schenk, S., Meikle, P. J., Horowitz, J. F., Kingwell, B. A., et al. (2012) · Diabetes · doi:10.2337/db12-0686 · Cited by 317
Metabolic Messengers: ceramides
Summers, S. A., Chaurasia, B., & Holland, W. L. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0134-8 · Cited by 312
Toll‐like receptors in alcoholic liver disease, non‐alcoholic steatohepatitis and carcinogenesis
Roh, Y. S., & Seki, E. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12019 · Cited by 309
The immune cells in adipose tissue
Ferrante, A. W. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12154 · Cited by 318
Macrophage infiltration into adipose tissue: initiation, propagation and remodeling
Surmi, B. K., & Hasty, A. H. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.545 · Cited by 307
Harford, K. A., Reynolds, C. M., McGillicuddy, F. C., & Roche, H. M. (2011) · Proceedings of The Nutrition Society · doi:10.1017/s0029665111000565 · Cited by 309
Inflammation in Alcoholic Liver Disease
Wang, H. J., Gao, B., Zakhari, S., & Nagy, L. E. (2012) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-072610-145138 · Cited by 298
Age-associated chronic diseases require age-old medicine: Role of chronic inflammation
Prasad, S., Sung, B., & Aggarwal, B. B. (2011) · Preventive Medicine · doi:10.1016/j.ypmed.2011.11.011 · Cited by 317
Ghanim, H., Sia, C. L., Upadhyay, M., Korzeniewski, K., Viswanathan, P., Abuaysheh, S., Mohanty, P., & Dandona, P. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28584 · Cited by 299
The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation
Kolb, H., & Mandrup-Poulsen, T. R. (2009) · Diabetologia · doi:10.1007/s00125-009-1573-7 · Cited by 299
Feeding Our Immune System: Impact on Metabolism
Wolowczuk, I., Verwaerde, C., Viltart, O., Delanoye, A., Delacre, M., Pot, B., & Grangette, C. (2008) · Clinical and Developmental Immunology · doi:10.1155/2008/639803 · Cited by 307
Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance
Jia, L., Vianna, C. R., Fukuda, M., Berglund, E. D., Liu, C., Tao, C., Sun, K., Liu, T., Harper, M. J., Lee, C. E., et al. (2014) · Nature Communications · doi:10.1038/ncomms4878 · Cited by 294
SirT1 regulates adipose tissue inflammation
Gillum, M. P., Kotas, M. E., Erion, D. M., Kursawe, R., Chatterjee, P., Nead, K. T., Muise, E. S., Hsiao, J. J., Frederick, D. W., Yonemitsu, S., et al. (2011) · Diabetes · doi:10.2337/db11-0616 · Cited by 260
Hersoug, L., Møller, P., & Loft, S. H. (2015) · Obesity Reviews · doi:10.1111/obr.12370 · Cited by 301
Yarandi, S., Peterson, D. A., Treisman, G. J., Moran, T. H., & Pasricha, P. J. (2016) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm15146 · Cited by 308
van Diepen, J. A., Berbée, J. F. P., Havekes, L. M., & Rensen, P. C. N. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.02.028 · Cited by 297
Trauner, M., Arrese, M. A., & Wagner, M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.10.007 · Cited by 302
Metadata
- Authors
- Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Flier, Jeffrey S.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-11-01
- Volume
- 116
- Issue
- 11
- Pages
- 3015-3025
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1616196
- OpenAlex
- W2156280702
- Cited by
- 3,690
- References
- 47
- Citations by year
- 2026: 126 · 2025: 131 · 2024: 135 · 2023: 140 · 2022: 167 · 2021: 176 · 2020: 209 · 2019: 180 · 2018: 206 · 2017: 243 · 2016: 220 · 2015: 259 · 2014: 222 · 2013: 274 · 2012: 252
- FWCI
- 86.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-R37-28082, R37DK028082)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- TLR4, lipopolysaccharide receptor, innate immunity, obesity, adipocytes, macrophages, inflammation, insulin signaling, glucose metabolism, high-fat diet, energy balance, TLR4-deficient mice
- MeSH terms
- Adipose Tissue, Animals, Cell Line, Fats, Fatty Acids, Female, Glucose, Humans, Immunity, Innate, Insulin Resistance, Macrophages, Muscles, Signal Transduction, Cytokines, NF-kappa B, Adipocytes, Genes, Reporter, Mice, Knockout, Toll-Like Receptor 4, Mice
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
