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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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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
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 ›
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