The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Open accessAbstract
Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
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“These cells produce high levels of TNFα, IL-6, and IL-1β, all of which are also observed in increased levels of adipose tissue from insulin resistant individuals.”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [70]
In the citing paper
“While the ATMs present in healthy lean adipose tissue are primarily of an M2 phenotype, those that accumulate in the adipose tissue during obesity have a strongly polarized pro-inflammatory, M1 phenotype [63,69–71].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [70]
In the citing paper
“However, two studies that investigated cellular markers of inflammation both reported an anti-inflammatory effect of vitamin D (747,748) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [747]
In the citing paper
“Using data pooled from thirty-six healthy subjects, twenty-four type 1 diabetics and twenty-six type 1 diabetics with microvascular complications, Devaraj et al. (747) found significant inverse relationships between serum 25(OH)D 3 and CRP concentration, monocyte NF-kB activation and TLR4 expression.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [747]
In the citing paper
“Accordingly, because of their proinflammatory properties, these macrophages are implicated in the pathogenesis of insulin resistance (103, 105, 112, 113).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [103]
In the citing paper
“The combination of microhypoxia and lipid overload triggers the recruitment of immune cells, such as macrophages in the adipose tissue and their activation ([103](#B103), [129](#B129), [171](#B171)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [103]
In the citing paper
“Under stimulation by B cells, effector T cells and Th1cells release cytokines such as interferon-γ to further stimulate activation of macrophages and induce a shift in macrophages from an M2-like phenotype to an M1-like phenotype.”
From The Vasculature in Prediabetes (2018) · cites this paper as [83]
In the citing paper
“In obese mice, a shift in the activation state of WAT macrophages from an M2 'alternatively activated' state to an M1 'pro-inflammatory state' was observed in response to diet-induced obesity [47].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [47]
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Metadata
- Authors
- Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Saltiel, Alan R.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-01-02
- Volume
- 117
- Issue
- 1
- Pages
- 175-184
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1716210
- OpenAlex
- W2145697808
- Cited by
- 4,664
- References
- 54
- Citations by year
- 2026: 157 · 2025: 214 · 2024: 227 · 2023: 224 · 2022: 256 · 2021: 324 · 2020: 320 · 2019: 304 · 2018: 290 · 2017: 322 · 2016: 296 · 2015: 290 · 2014: 286 · 2013: 319 · 2012: 226
- FWCI
- 92.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan
- National Institutes of Health (HD028820)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK60591, R01DK060591)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007513, K12HD028820)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- obesity, adipose tissue macrophages, macrophage polarization, M1/M2 macrophages, insulin resistance, diet-induced obesity, CCR2, IL-10, TNF-α, adipocyte inflammation, high-fat diet, M2 macrophages
- MeSH terms
- Adipose Tissue, Animals, Base Sequence, Biological Transport, Energy Intake, Deoxyglucose, Dietary Fats, Disease Models, Animal, Macrophages, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, 3T3 Cells, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Mice
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