Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals
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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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Conditional ablation of CD11c+ macrophages in the adipose tissue of high-fat-diet-fed obese mice results in a profound reduction of proinflammatory ATM accumulation, accompanied by rapid whole-body normalization of insulin sensitivity.
“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]
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.
“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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Self-citation
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › 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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