The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals
Open accessAbstract
Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance. Here, we used a conditional cell ablation system, based on transgenic expression of the diphtheria toxin receptor under the control of the CD11c promoter, to study the effects of depletion of CD11c+ cells in obese mouse models. Our results show that CD11c+ cell depletion results in rapid normalization of insulin sensitivity. Furthermore, CD11c+ cell ablation leads to a marked decrease in inflammatory markers, both locally and systemically, as reflected by gene expression and protein levels. Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes.
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“Such conditional ablation resulted in a profound reduction of proinflammatory ATM accumulation, accompanied by rapid whole-body normalization of insulin sensitivity (43).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [43]
In the citing paper
“M1-like macrophages secrete inflammatory cytokines such as TNF-α and IL-6, and studies in M1-like macrophage knockout mice suggest they also promote insulin resistance.”
From The Vasculature in Prediabetes (2018) · cites this paper as [84]
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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 · cited 3×
“…shown that obesity is associated with increased macrophage content in skeletal muscle, including CD11c+ cells, and this muscle macrophage accumulation is accompanied by increased expression of inflammatory factors in muscle (Hevener et al., 2007; Nguyen et al., 2007; Weisberg et al., 2003).”
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · cited 1×
“Resident tissue macrophages display tremendous heterogeneity in their activities and functions, primarily reflecting the local metabolic and immune microenvironment (Gordon and Taylor, 2005; Mantovani et al., 2004).”
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · cited 1×
“Resident tissue macrophages display tremendous heterogeneity in their activities and functions, primarily reflecting the local metabolic and immune microenvironment (Gordon and Taylor, 2005; Mantovani et al., 2004).”
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · cited 10×
“These results suggest that the source of the IL-10 in the DT treated CD11c-DTR BMT mice are the remaining CD11c ATMs (Cancello et al., 2005; Lumeng et al., 2007).”
InfluentialKim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061
Kanda, H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26498 · Cited by 2,682 · cited 4×
“…in ATMs is associated with a decrease in adipose tissue inflammation and a reduction in obesityinduced insulin resistance (Ellacott et al., 2007; Kanda et al., 2006; Lesniewski et al., 2007; Nara et al., 2007; Neels and Olefsky, 2006; Nomiyama et al., 2007; Weisberg et al., 2006), while an…”
InfluentialCinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529 · cited 2×
“Previously, ATMs were shown to cluster around dead adipocytes in so-called crown-like structures (CLS; (Cinti et al., 2005; Strissel et al., 2007), and CD11c+ cells are localized to these ATM clusters (Lumeng et al., 2007).”
Jung, S., Unutmaz, D., Wong, P., Sano, G., Santos, K. D. L., Sparwasser, T., Wu, S., Vuthoori, S., Ko, K., Zavala, F., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00365-5 · Cited by 1,953 · cited 3×
“While transient DC depletion was not associated with signs of illness or long-term defects, repeated DT induction is lethal to the mouse (Jung et al., 2002).”
InfluentialObesity, Inflammation, and Insulin Resistance
Shoelson, S. E., Herrero, L., & Naaz, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.059 · Cited by 1,806 · cited 4×
“In both humans and rodents, adipose tissue macrophages (ATMs) accumulate in adipose tissue (AT) with increasing body weight, and evidence is mounting that implicates ATMs as a significant contributor to inflammation in obesity and a mediator of IR (Shoelson et al., 2007).”
InfluentialIKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
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Etude du rôle des sous-populations monocytaires dans l'obésité et l'insulinorésistance
Béliard, S. (2011) · OpenGrey (Institut de l'Information Scientifique et Technique)
Metadata
- Authors
- Patsouris, D., Li, P.-P., Thapar, D., Chapman, J., Olefsky, J. M., & Neels, J. G.
- Affiliations
- University of California San Diego (US)
- Pfizer (United States) (US)
- Corresponding author
- Neels, Jaap G.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 8
- Issue
- 4
- Pages
- 301-309
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2630775
- OpenAlex
- W2011255130
- Cited by
- 804
- References
- 34
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 24 · 2023: 31 · 2022: 29 · 2021: 65 · 2020: 45 · 2019: 47 · 2018: 52 · 2017: 60 · 2016: 62 · 2015: 60 · 2014: 70 · 2013: 70 · 2012: 50
- FWCI
- 25.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Moores Cancer Center, UC San Diego Health
- University of California, San Diego
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 074868, DK 033651, R37DK033651, P01DK074868, R01DK033651)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD012303, HD012303, U54HD012303)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- CD11c+ macrophages, obesity, insulin resistance, adipose tissue macrophages, macrophage depletion, diphtheria toxin receptor, inflammation, type 2 diabetes, therapeutic target
- MeSH terms
- Adipose Tissue, Animals, Glucose, Homeostasis, Humans, Insulin, Insulin Resistance, Liver, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Obesity, Gene Expression, Cytokines, Chemokines, Chemokine CCL2, Intercellular Signaling Peptides and Proteins, CD11c Antigen, Mice, Heparin-binding EGF-like Growth Factor
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