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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.
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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]
Experimental — accuracy not yet measuredThe 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
“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]
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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
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Cani, P. D., & Everard, A. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500406 · Cited by 181
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Phillips, L. K., & Prins, J. B. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0029-7 · Cited by 178
Macrophages and Adipocytes in Human Obesity
Capel, F., Klimčáková, E., Viguerie, N., Roussel, B., Šiklová, M., Kováčiková, M., Polak, J., Kováčová, Z., Galitzky, J., Maoret, J.-J., et al. (2009) · Diabetes · doi:10.2337/db09-0033 · Cited by 180
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Henao‐Mejia, J., Elinav, E., Thaiss, C. A., & Flavell, R. A. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170324 · Cited by 176
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Naz, R., Saqib, F., Awadallah, S. M., Wahid, M., Latif, M. F., Iqbal, I., & Mubarak, M. S. (2023) · Molecules · doi:10.3390/molecules28103996 · Cited by 178
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Cai, W., He, C., Zhu, L., Chen, X., Wallenstein, S. R., Striker, G. E., & Vlassara, H. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.061281 · Cited by 177
Chistiakov, D. A., Bobryshev, Y. V., Nikiforov, N. G., Elizova, N. V., Sobenin, I. A., & Orekhov, A. N. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.03.055 · Cited by 184
RetractedSingh, V., Chassaing, B., Zhang, L., Yeoh, B. S., Xiao, X., Kumar, M., Baker, M. T., Cai, J., Walker, R. E., Borkowski, K., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.028 · Cited by 179
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Reinhardt, C., Reigstad, C. S., & Bäckhed, F. (2009) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e318183187c · Cited by 180
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Orr, J. S., Puglisi, M. J., Ellacott, K. L. J., Lumeng, C. N.-K., Wasserman, D. H., & Hasty, A. H. (2012) · Diabetes · doi:10.2337/db11-1595 · Cited by 173
Ahmad, R., Al‐Mass, A., Atizado, V., Alhubail, A., Al-Ghimlas, F., Alarouj, M., Bennakhi, A., Dermime, S., & Behbehani, K. (2012) · Journal of Inflammation · doi:10.1186/1476-9255-9-48 · Cited by 171
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Bhattacharyya, S., Gill, R. K., Chen, M. L., Zhang, F., Linhardt, R. J., Dudeja, P. K., & Tobacman, J. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708833200 · Cited by 170
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Renz, H., von Mutius, E., Brandtzæg, P., Cookson, W., Autenrieth, I. B., & Haller, D. (2011) · Nature Immunology · doi:10.1038/ni0411-273 · Cited by 172
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Shah, R. D., Hinkle, C. C., Ferguson, J. F., Mehta, N. N., Li, M., Qu, L., Lu, Y., Putt, M., Ahima, R. S., & Reilly, M. P. (2011) · Diabetes · doi:10.2337/db10-0956 · Cited by 174
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Vinolo, M. A. R., Rodrigues, H. G., Festuccia, W. T., Crisma, A. R., Alves, V. S., Martins, A. R., do Amaral, C. L., Fiamoncini, J., Hirabara, S. M., Sato, F. T., et al. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00053.2012 · Cited by 173
Brown, J. M., Chung, S., Sawyer, J. K., Degirolamo, C., Alger, H. M., Nguyen, T., Zhu, X., Duong, M., Wibley, A. L., Shah, R., et al. (2008) · Circulation · doi:10.1161/circulationaha.108.793182 · Cited by 169
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Moya, M. D. L. L., McGillicuddy, F. C., Hinkle, C. C., Byrne, M., Joshi, M. R., Nguyen, V., Tabita‐Martinez, J., Wolfe, M. L., Badellino, K. O., Pruscino, L., et al. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.02.032 · Cited by 171
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Nogueira‐Machado, J. A., Volpe, C. M. O., Veloso, C. A., & Chaves, M. M. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.575360 · Cited by 172
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Vlassara, H., & Striker, G. E. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.07.005 · Cited by 171
Karamali, M., Dadkhah, F., Sadrkhanlou, M., Jamilian, M., Ahmadi, S., Ebrahimi, M. T., Jafari, P., & Asemi, Z. (2016) · Diabetes & Metabolism · doi:10.1016/j.diabet.2016.04.009 · Cited by 170
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Li, S., Sun, Y., Liang, C., Thorp, E. B., Han, S., Jehle, A. W., Saraswathi, V., Pridgen, B. C., Kanter, J. E., Li, R., et al. (2009) · Circulation Research · doi:10.1161/circresaha.109.199570 · Cited by 173
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Ono, Y., Maejima, Y., Saito, M., Sakamoto, K., Horita, S., Shimomura, K., Inoue, S., & Kotani, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-57714-3 · Cited by 169
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Elks, C. M., & Francis, J. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0096-4 · Cited by 170
Vila, I. K., Badin, P.-M., Marques, M.-A., Monbrun, L., Lefort, C., Mir, L., Louche, K., Bourlier, V., Roussel, B., Gui, P., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.062 · Cited by 165
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Shu, C. J., Benoist, C. O., & Mathis, D. J. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.001 · Cited by 170
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Jiao, P., Chen, Q., Shah, S., Du, J., Bo, T., Tzameli, I., Yan, W., & Xu, H. (2008) · Diabetes · doi:10.2337/db07-1344 · Cited by 171
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Veldhoen, M., & Brucklacher-Waldert, V. (2012) · Nature reviews. Immunology · doi:10.1038/nri3299 · Cited by 167
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van Ton, A. M. P., Kox, M., Abdo, W. F., & Pickkers, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01926 · Cited by 167
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Reilly, S. M., & Lee, C.-H. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.040 · Cited by 164
Morton, N. M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.024 · Cited by 169
Ozaki, K., Awazu, M., Tamiya, M., Iwasaki, Y., Harada, A., Kugisaki, S., Tanimura, S., & Kohno, M. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00445.2015 · Cited by 169
Fang, W., Xue, H., Chen, X., Chen, K., & Ling, W. (2019) · Journal of Nutrition · doi:10.1093/jn/nxy324 · Cited by 168
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Rao, S. R. (2012) · Inflammation Research · doi:10.1007/s00011-012-0473-3 · Cited by 162
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Remely, M., Tesar, I., Hippe, B., Gnauer, S., Rust, P., & Haslberger, A. G. (2015) · Beneficial Microbes · doi:10.3920/bm2014.0104 · Cited by 162
Karasawa, T., Kawashima, A., Usui-Kawanishi, F., Watanabe, S., Kimura, H., Kamata, R., Shirasuna, K., Koyama, Y., Sato-Tomita, A., Matsuzaka, T., et al. (2018) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.117.310581 · Cited by 162
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Laugerette, F., Vors, C., Peretti, N., & Michalski, M. (2010) · Biochimie · doi:10.1016/j.biochi.2010.04.016 · Cited by 170
Jounai, N., Kobiyama, K., Takeshita, F., & Ishii, K. J. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00168 · Cited by 169
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Liu, X., Lu, B., Fu, J., Zhu, X., Song, E., & Song, Y. (2020) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2020.124050 · Cited by 167
Wang, X.-A., Zhang, R., She, Z., Zhang, X., Jiang, D.-S., Wang, T., Gao, L., Deng, W., Zhang, S., Zhu, L., et al. (2013) · Hepatology · doi:10.1002/hep.26751 · Cited by 163
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Liu, H.-Q., Qiu, Y. F., Mu, Y., Zhang, X.-J., Liu, L., Hou, X.-H., Zhang, L., Xu, X., Ji, A.-L., Cao, R., et al. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.07.004 · Cited by 165
Ungaro, R., Fukata, M., Hsu, D., Hernandez, Y., Breglio, K., Chen, A., Xu, R., Sotolongo, J., Espana, C., Zaias, J., et al. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90496.2008 · Cited by 159
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Furusho, H., Miyauchi, M., Hyogo, H., Inubushi, T., Ao, M., Ouhara, K., Hisatune, J., Kurihara, H., Sugai, M., Hayes, C. N., et al. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-012-0738-1 · Cited by 157
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Ko, H. J., Zhang, Z., Jung, D. Y., Jun, J. Y., Ma, Z., Jones, K. E., Chan, S. Y., & Kim, J. K. (2009) · Diabetes · doi:10.2337/db08-1361 · Cited by 160
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Han, J. M., & Levings, M. K. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301035 · Cited by 162
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Kohlgruber, A. C., & Lynch, L. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0670-x · Cited by 163
Toll-like receptors regulate B cell cytokine production in patients with diabetes
Jagannathan, M., McDonnell, M., Liang, Y., Hasturk, H., Hetzel, J., Rubin, D., Kantarci, A., Van Dyke, T. E., Ganley-Leal, L. M., & Nikolajczyk, B. S. (2010) · Diabetologia · doi:10.1007/s00125-010-1730-z · Cited by 156
Circulating Palmitoleate Strongly and Independently Predicts Insulin Sensitivity in Humans
Stefan, N., Kantartzis, K., Celebi, N., Staiger, H., Machann, J., Schick, F., Čegan, A., Elcnerova, M., Schleicher, E. D., Fritsche, A., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0544 · Cited by 156
Pathophysiologic Response to Burns in the Elderly
Jeschke, M. G., Patsouris, D., Stanojcic, M., Abdullahi, A., Rehou, S., Pinto, R. L., Chen, P., Burnett, M., & Amini‐Nik, S. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.07.040 · Cited by 157
Zu, L., He, J., Jiang, H., Xu, C. B., Pu, S., & Xu, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807852200 · Cited by 155
Rahman, S. M., Schroeder‐Gloeckler, J. M., Janssen, R. C., Jiang, H., Qadri, I., Maclean, K. N., & Friedman, J. E. (2007) · Hepatology · doi:10.1002/hep.21614 · Cited by 159
Effect of the dietary fat quality on insulin sensitivity
Galgani, J. E., Uauy, R. D., Aguirre, C. A., & Díaz, E. O. (2008) · British Journal of Nutrition · doi:10.1017/s0007114508894408 · Cited by 154
Phenotypic modulation of macrophages in response to plaque lipids
Adamson, S., & Leitinger, N. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834a97e4 · Cited by 154
Romanatto, T., Roman, E. A., Arruda, A. P., Denis, R., Solon, C., Milanski, M., Moraes, J. C., Bonfleur, M. L., Degasperi, G. R., Picardi, P. K., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.030874 · Cited by 156
RetractedInsulin Resistance and Mitochondrial Dysfunction
González-Franquesa, A., & Patti, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_25 · Cited by 160
Nonalcoholic fatty liver disease: A main driver of insulin resistance or a dangerous liaison?
Gruben, N., Shiri‐Sverdlov, R., Koonen, D. P. Y., & Hofker, M. H. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.08.004 · Cited by 156
Interleukin-1 Receptor Antagonist: A New Therapy for Type 2 Diabetes Mellitus
Akash, M. S. H., Shen, Q., Rehman, K., & Chen, S. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23057 · Cited by 158
PPARγ in the endothelium regulates metabolic responses to high-fat diet in mice
Kanda, T., Brown, J. D., Orasanu, G., Vogel, S., Gonzalez, F. J., Sartoretto, J. L., Michel, T. M., & Plutzky, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36233 · Cited by 160
Genome-wide association study for intramuscular fat deposition and composition in Nellore cattle
César, A. S. M., Regitano, L. C. D. A., Mourão, G. B., Túllio, R. R., Lanna, D. P., NASSU, R. T., Mudadu, M. A., Oliveira, P. S., do Nascimento, M. L., Chaves, A. S., et al. (2014) · BMC Genetics · doi:10.1186/1471-2156-15-39 · Cited by 152
Pathophysiological role of host microbiota in the development of obesity
Kobyliak, N. M., Virchenko, O., & Falalyeyeva, T. M. (2015) · Nutrition Journal · doi:10.1186/s12937-016-0166-9 · Cited by 156
Ischemic Retinopathies: Oxidative Stress and Inflammation
Rivera, J. C., Dabouz, R., Noueihed, B., Omri, S., Tahiri, H., & Chemtob, S. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3940241 · Cited by 153
Obesity, Inflammation, and Prostate Cancer
Fujita, K., Hayashi, T., Matsushita, M., Uemura, M., & Nonomura, N. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8020201 · Cited by 158
Portincasa, P., Khalil, M., Mahdi, L., Perniola, V., Idone, V., Graziani, A., Baffy, G., & Ciaula, A. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115640 · Cited by 167
Elevated Muscle TLR4 Expression and Metabolic Endotoxemia in Human Aging
Ghosh, S., Lertwattanarak, R., Garduno, J. D. J., Galeana, J. J., Li, J., Zamarripa, F., Lancaster, J. L., Mohan, S., Hussey, S., & Musi, N. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu067 · Cited by 150
Miura, K., Seki, E., Ohnishi, H., & Brenner, D. A. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/362847 · Cited by 152
Adipose tissue recruitment of leukocytes
Anderson‐Baucum, E. K., Gutierrez, D. A., & Hasty, A. H. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283393867 · Cited by 156
Wu, C., Jain, D., McNeill, J. N., Little, D., Anderson, J. A. D., Huebner, J. L., Kraus, V. B., Rodriguiz, R. M., Wetsel, W. C., & Guilak, F. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-205601 · Cited by 150
Dorenkott, M. R., Griffin, L. E., Goodrich, K. M., Thompson‐Witrick, K. A., Fundaro, G., Ye, L., Stevens, J. R., Ali, M. M., O’Keefe, S. F., Hulver, M. W., et al. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf500333y · Cited by 153
Zhang, T., Chen, J., Tang, X., Luo, Q., Xu, D., & Yu, B. (2019) · Lipids in Health and Disease · doi:10.1186/s12944-019-1170-9 · Cited by 163
Mohseni, S., Bayani, M., Bahmani, F., Ebrahimi, M. T., Bayani, M. A., Jafari, P., & Asemi, Z. (2017) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2970 · Cited by 152
Arafah, A. M., Rehman, M. U., Mir, T. M., Wali, A. F., Ali, R., Qamar, W., Khan, R., Ahmad, A., Aga, S. S., Alqahtani, S., et al. (2020) · Plants · doi:10.3390/plants9121784 · Cited by 149
The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease
Gill, P. A., Inniss, S., Kumagai, T., Rahman, F. Z., & Smith, A. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.866059 · Cited by 164
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
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