The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4 Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-Fed Mice
Open accessAbstract
Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4(-/-)) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4(-/-) mice became obese but did not develop fasting hyperinsulinemia and had improved hepatic and adipose insulin sensitivity during euglycemic clamp studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4(-/-) mice also showed markedly reduced adipose tissue inflammatory markers and macrophage content. In summary, our results indicate that Tlr4 signaling in hematopoietic-derived cells is important for the development of hepatic and adipose tissue insulin resistance in obese mice.
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?
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 [77]
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
1 retracted
Tsukumo, D. M. L., Carvalho-Filho, M. A., Carvalheira, J. B. C., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A., et al. (2007) · Diabetes · doi:10.2337/db06-1595 · Cited by 826 · cited 12×
“These findings are comparable to the results of Tsukomo et al. (2007).”
BackgroundInfluentialRetractedA SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · cited 1×
“The triacylglycerol (TAG) and diacyglycerol (DAG) levels in liver and muscle cell lysates were determined using 50–100 mg of tissue, subjected to lipid extraction by organic solvents as previously described by Bligh and Dyer (1959) and Folch et al. (1957).”
MethodA RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751 · cited 1×
“The triacylglycerol (TAG) and diacyglycerol (DAG) levels in liver and muscle cell lysates were determined using 50–100 mg of tissue, subjected to lipid extraction by organic solvents as previously described by Bligh and Dyer (1959) and Folch et al. (1957).”
MethodObesity 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 · cited 5×
“It is likely that the reduced expression of TNF-a is directly related to the reduced macrophage infiltration, as macrophages are the primary source of TNF-a in obese adipose tissue (Weisberg et al., 2003; Xu et al., 2003).”
BackgroundInfluentialDefective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · cited 2×
“Hematopoietic Deletion of Tlr4 Does Affect Peripheral Lineage Distributions To generate mice with a complete knockout of Tlr4 in macrophages and other immune cells, we transplanted irradiated wild-type (WT) C57BL6 mice with bone marrow from Tlr4 (Poltorak et al., 1998) or WT C57BL/10J mice.”
BackgroundMethodXu, 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 · cited 5×
“It is likely that the reduced expression of TNF-a is directly related to the reduced macrophage infiltration, as macrophages are the primary source of TNF-a in obese adipose tissue (Weisberg et al., 2003; Xu et al., 2003).”
BackgroundInfluentialTLR4 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 · cited 13×
“In addition, obesity due to high-fat diet (HFD) feeding and insulin resistance caused by a lipid-plus-heparin infusion were etabolism 10, 419–429, November 4, 2009 ª2009 Elsevier Inc. 419 attenuated in Tlr4 knockout mice, in parallel with decreased inflammation in both liver and adipose tissue (Shi et al., 2006; Tsuku…”
BackgroundResultInfluentialA Third-Generation Lentivirus Vector with a Conditional Packaging System
Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341 · cited 6×
“To ensure high-level transduction efficiency in the bone marrow cells, we included the marker gene GFP in both vectors.”
MethodInfluentialDevelopment of T H 1 CD4 + T Cells Through IL-12 Produced by Listeria -Induced Macrophages
Hsieh, C.-S., Macatonia, S. E., Tripp, C. S., Wolf, S. F., O'Garra, A., & Murphy, K. M. (1993) · Science · doi:10.1126/science.8097338 · Cited by 3,134 · cited 1×
“It is notable that IL-12 p70 was reduced in our mice because IL-12 is important for the transition of naive T cells into Th1 cells (Hsieh et al., 1993).”
BackgroundToll-like receptors in the induction of the innate immune response
Aderem, A. A., & Ulevitch, R. J. (2000) · Nature · doi:10.1038/35021228 · Cited by 3,082 · cited 1×
“The ‘‘sensors’’ that potentially link obesity to inflammation are the Toll-like family of receptors (Tlrs); Tlrs are pattern recognition receptors that play critical roles in innate immunity (Aderem and Ulevitch, 2000; Wolowczuk et al., 2008).”
Background
Cited by
Sorted by citations
Items 401–454 of 454
Bolton, J. L. (2015) · DukeSpace (Duke University)
TGF-β and Metabolic Homeostasis
Bennett, G., & Rane, S. G. (2013) · Springer eBooks · doi:10.1007/978-4-431-54409-8_18
Gagliardi, C. F. (2021) · Scholarworks (University of Massachusetts Amherst) · doi:10.7275/5768694
Role of immune mediators in metabolic syndrome and atherosclerosis
Strodthoff, D. (2013) · Figshare
The Role of Diet in Inflammation and Metabolic Syndrome
Sears, B. (2015) · Springer eBooks · doi:10.1007/978-3-319-16853-1_1
Cooper, A. W. J. (2013) · PEARL (University of Plymouth) · doi:10.24382/4356
TLR4 in bone marrow-derived cells mediates obesity-induced insulin resistance
(2015) · Immunoendocrinology · doi:10.14800/ie.454
Obesidade: um enfoque na inflamação periférica e central
Fróes, F. T. (2012) · Lume (Universidade Federal do Rio Grande do Sul)
Bad Fat or Just More Fat? Murine Models of Metabolically Healthy Obesity
Bennett, G., Greenberg, A. S., & Obin, M. S. (2014) · Humana Press eBooks · doi:10.1007/978-1-62703-770-9_4 · Cited by 1
Zhu, X., Zong, G., Liu, Z., Jiang, Y., Ma, K., Zhang, H., Zhang, Y., Bai, H., Yang, Q., Ben, J., et al. (2013)
Novel insights into the function and regulation of group X secretory phospholipase A 2
Layne, & Joseph, D. (2013) · UKnowledge (University of Kentucky)
Gut Flora in the Development and Progression of Nonalcoholic Fatty Liver Disease
Okwu, V., & Matloob, A. (2015) · Journal of Liver Disease & Transplantation · doi:10.4172/2325-9612.1000128
Mechanisms Mediating Obesity-Induced Inflammation and Insulin Resistance
Schenk, S., Osborn, O., & Olefsky, J. M. (2011) · CRC Press eBooks · doi:10.1201/b11294-14
Self-citationPalmitic Acid Activation of Dendritic Cells: Implications for Type 2 Diabetes
Nicholas, D. (2015) · The Scholars Repository - LLU (Loma Linda University)
Macrophages Are Regulators of Whole Body Metabolism: A Dissertation
Yawe, J. C. (2016) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2d30w
“Obese rodents and humans exhibit increased systemic LPS levels, and interfering with TLR4 signaling ameliorates ATM accumulation and M1 polarization (140, 141).”
BackgroundStudies on the Development and Consequences of Neuroinflammation in Obesity
Buckman, L. B. (2014)
Insulin receptor sensitization improves affective pathology in various mouse models
Nunes, J. P. D. C. A. V. (2015) · doi:10.26481/dis.20151221jc
Nagai, Y., Watanabe, Y., Honda, H., & Takatsu, K. (2017) · InTech eBooks · doi:10.5772/66727 · Cited by 1
Tilves, C. (2017) · D-Scholarship@Pitt (University of Pittsburgh)
THE ROLE OF THE INTESTINAL MICROBIOTA IN THE MODULATION OF FOOD INTAKE AND BODY WEIGHTPreprint
Dalby, M. J. (2017) · Thesis Commons (OSF Preprints) · doi:10.31237/osf.io/rqz2p
An Insight into the Changing Scenario of Gut Microbiome during Type 2 Diabetes
Mukhuty, A., Fouzder, C., Das, S., & Chattopadhyay, D. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.90697
Cardiometabolic Risk and Epicardial Adipose Tissue
Iacobellis, G., & Fricke, A. C. V. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-40570-0_13
Study of Toll-like Receptors 4 in Type 2 Diabetic Patients with and without nephropathy
Fathy, W. M., Soliman, M. A., & Ragheb, A. (2015)
Deng, Q., Du, L., Zhang, Y., & Liu, G. (2021) · Research Square · doi:10.21203/rs.3.rs-553323/v1
Taub, D. D., & Lustig, A. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717949620.793454826
Uncoupling of fat deposition and inflammation during nonalcoholic fatty liver disease
Li, H., Guo, X., Aquino, E., & Wu, C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95582-9.00012-7
Body fat distribution and obesity
Lempesis, I. G. (2023) · Research Publications (Maastricht University) · doi:10.26481/dis.20231019ll · Cited by 1
Potent inflammatory biomarkers in insulin resistance
Verma, S., Abbas, M., Talwar, A., Anand, S., Nayyar, A., Fatima, F., & Zahera, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13195-0.00012-0
Jeelani, I., da Cunha, F. F., Rohm, T. V., Nasamran, C. A., Moon, J.-S., Wang, L., Prakash, S., Issac, R., Murphy, C., Glass, C. K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.20.670151
Self-citationLan, Y., Wu, D., Zheng, H., Ding, X., Zhou, H., Wu, K., Wu, W., Huang, Z., Wang, X., Wang, W., et al. (2025) · Journal of Global Health · doi:10.7189/jogh.15.04318
“…and short-term duration that may confound the elevation of the real effect of anti-inflammation on preventing diabetes, the consistent reduction in overall inflammation during the treatment and overall positive effect on improving β-cell biology and glucose hemostasis was suggested [ 18 , 19 ].”
Liu, M., Zhou, K., Yang, S. Y., Zhang, W., Chen, Q., Chen, Z., Yang, X., Jin, Y., Liu, F., Mu, Y., et al. (2025) · Science China Life Sciences · doi:10.1007/s11427-025-2957-9
“Both germ-line and hematopoietic-specific deletion of TLR4 ameliorate obesity-associated insulin resistance (Saberi et al., 2009; Shi et al., 2006).”
Microbial Dysbiosis and Metabolic Disorder
Kesavardhini, K., Saranraj, P., Subhalakshmi, U., Gayathri, K., & Lokeshwari, B. (2026) · IGI Global eBooks · doi:10.4018/979-8-3373-4382-2.ch008
Vasudevan, D. (2026) · World Journal of Diabetes · doi:10.4239/wjd.v17.i3.113843
Tersigni, C., Beneduce, G., Onori, M., Sannino, F., Petrecca, A., Simone, N. D., & Ghi, T. (2026) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2026.2647317
Inflammation du tissu adipeux au cours de l'obésité humaine : implication des lymphocytes Th17
Caër, C. (2016) · theses.fr (ABES) · doi:10.70675/65eca5dczaa63z4e9az82dbzb223bfe8ef82 · Cited by 1
Amine, H. (2016) · theses.fr (ABES) · doi:10.70675/8fc153dfzc95cz4209zabf7z1567442c940d
“Les souris déficientes en TLR4 sont protégées contre l’obésité et la résistance à l’insuline induites par un régime hyperlipidique ou par un traitement par des acides gras saturés (Saberi et al., 2009; Shi et al., 2006).”
Étude du rôle du transporteur de phosphate inorganique PiT1/SLC20A1 dans l'inflammation
Koumakis, E. (2016) · theses.fr (ABES) · doi:10.70675/7bdb44faz8800z4b6dz9e92zce56d29c4f27
Rôle de la mPGES-1 dans le développement de l'inflammation chronique de bas seuil et de l'obésité
Clément, P. (2018) · theses.fr (ABES) · doi:10.70675/03fb1889z1609z4461z931dze2b1aebfa2b6
The role of TLR7 in Sjögren's syndrome
Wang, Y. (2020) · theses.fr (ABES) · doi:10.70675/69155cbezc742z41b7za0f6z2b1f895a26dd
Rôle des macrophages dans le remodelage pathologique du tissu adipeux au cours de l'obésité
Askia, H. (2022) · theses.fr (ABES) · doi:10.70675/0d09beffzcdaez4950za6c0z29a0dd68a41b
Lipid rewiring by adipose tissue macrophages during diet-induced inflammation and insulin resistance
Dahik, V. D. (2023) · theses.fr (ABES) · doi:10.70675/8f4f001ez6ebez4d7az934bz039a1f4d4116
Xu, Z., Sun, Z., Wang, F., Han, Q., Li, S., Xue, C., Li, Y., Liu, D., Cai, J., & Sun, H. (2026) · Foods · doi:10.3390/foods15091508
“ITT mainly reflects insulin sensitivity in peripheral tissues such as muscle and adipose tissue; therefore, the observed improvement suggests that SHY0006 may enhance insulin responsiveness and glucose utilization in peripheral tissues [33].”
The Pathophysiology of Obesity and Obesity-Related Diseases
Bozadjieva-Kramer, N., & O’Rourke, R. W. (2026) · Springer eBooks · doi:10.1007/978-3-032-24278-5_6
Toll-like receptor 4 knockout mice are protected against PMOS-like pathogenesis
Wiggins, K. D., Mundo, Z. D. D., Angulo, J. A. A., Naidu, N., Saba, A., Zhou, L., Garcia, C., Nguyen, C. M., Ujagar, N. S., Torre, J.-J. D. L., et al. (2026) · Reproduction · doi:10.1093/reprod/xaag081
Research Progress on the Action of Immune Cells in Metabolic Syndrome
陈, 翀. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1672537
Cai, Z., Wen, X., Wu, H., & Luo, Y. (2026) · Clinical & Translational Metabolism · doi:10.1007/s12018-026-09337-x
“Saberi et al. [ 20] demonstrated through bone marrow transplantation experiments that hematopoietic cell-specific deletion of TLR4 significantly ameliorates hepatic and adipose tissue insulin resistance in high-fat diet (HFD)-fed mice, indicating that TLR4 expressed in immune cells serves as a key…”
Wei, W., Wang, D., Han, X., Cui, Y., Sun, X., Li, L., Ni, Y., & Jiang, M. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117599
Immunomodulatory Pathways and Metabolism
Bhargava, P. (2013) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Metadata
- Authors
- Saberi, M., Woods, N.-B., de Luca, C., Schenk, S., Lu, J. C., Bandyopadhyay, G., Verma, I. M., & Olefsky, J. M.
- Affiliations
- University of California San Diego (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Olefsky, Jerrold M.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 10
- Issue
- 5
- Pages
- 419-429
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2790319
- OpenAlex
- W2010911569
- Cited by
- 456
- References
- 26
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 15 · 2023: 11 · 2022: 17 · 2021: 20 · 2020: 27 · 2019: 21 · 2018: 35 · 2017: 24 · 2016: 28 · 2015: 35 · 2014: 34 · 2013: 60 · 2012: 46
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Lustgarten Foundation
- National Institutes of Health (DK033651, T32 DK 007494, DK074868, U54 HD 012303-25)
- Ellison Medical Foundation
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TLR4, insulin resistance, obesity, high-fat diet, bone marrow transplantation, hepatic insulin sensitivity, adipose tissue inflammation, macrophages, low-grade inflammation, hyperinsulinemia, impaired glucose tolerance
- MeSH terms
- Adipose Tissue, Animals, Dietary Fats, Hematopoietic Stem Cells, Insulin Resistance, Liver, Macrophages, Mice, Obese, Obesity, Organ Specificity, Glucose Clamp Technique, Signal Transduction, Glucose Intolerance, Toll-Like Receptor 4, Mice, Gene Knockout Techniques
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
