Obesity induces a phenotypic switch in adipose tissue macrophage polarization

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 F4/8...

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Bibliographic Details
Published in:The Journal of clinical investigation 2007-01, Vol.117 (1), p.175-184
Main Authors: Lumeng, Carey N, Bodzin, Jennifer L, Saltiel, Alan R
Format: Article
Language:English
Subjects:
3T3 Cells
Adipocytes
Adipose Tissue - pathology
Adipose Tissue - physiopathology
Adipose tissues
Animals
Base Sequence
Biological Transport
Biomedical research
Body fat
Chemokines
Cytokines
Deoxyglucose - metabolism
Diabetes
Dietary Fats
Disease Models, Animal
DNA Primers
Energy Intake
Flow cytometry
Inflammation
Insulin resistance
Kinases
Macrophages - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Obesity - genetics
Obesity - physiopathology
Reverse Transcriptase Polymerase Chain Reaction
Risk factors
Weight control
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci29881