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Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Carey N. Lumeng, … , Jennifer L. Bodzin, Alan R. Saltiel
Carey N. Lumeng, … , Jennifer L. Bodzin, Alan R. Saltiel
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):175-184. https://doi.org/10.1172/JCI29881.
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Research Article

Obesity induces a phenotypic switch in adipose tissue macrophage polarization

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Abstract

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-α 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-α–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.

Authors

Carey N. Lumeng, Jennifer L. Bodzin, Alan R. Saltiel

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Figure 7

IL-10 prevents the effects of TNF-α on blocking insulin-stimulated glucose uptake in adipocytes.

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IL-10 prevents the effects of TNF-α on blocking insulin-stimulated gluco...
(A) Pretreatment of adipocytes with IL-10 blocks TNF-α effects on glucose uptake. 3T3-L1 adipocytes were treated with IL-10 (20 ng/ml) for 24 hours prior to treatment with TNF-α (17 ng/ml) for 3 hours. 2-Deoxyglucose (2-DG) uptake was assessed after 30 minutes without (white bars) or with (black bars) insulin (100 nM) stimulation. Data are expressed as mean ± SD of triplicate experiments repeated 3 times. *P < 0.05. (B) Insulin-stimulated glucose uptake in adipocytes chronically treated with IL-10 and TNF-α. Differentiated 3T3-L1 adipocytes were treated with low-dose TNF-α (3 ng/ml) for 72 hours in the presence or absence of IL-10 (20 ng/ml). After insulin stimulation (black bars), 2-DG uptake (upper panel) and fold change in glucose uptake (lower panel) were assessed, and the results demonstrated that IL-10 blocks the effects of TNF-α. Data are expressed as mean ± SD of triplicate experiments repeated 2 times. *P < 0.05.

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