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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 1

Accumulation of F4/80+CD11c+ ATMs in adipose tissue in obese mice.

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Accumulation of F4/80+CD11c+ ATMs in adipose tissue in obese mice.
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(A) Analysis of SVF cells for F4/80 and CD11c. Epididymal fat pads from age-matched male C57BL/6 (C57) mice on ND or HFD (n = 3 mice, each condition) were dissected and separated into adipocyte and SVF populations. SVF cells were stained with antibodies against F4/80, CD11c, and isotype controls (open) and analyzed by flow cytometry. Samples were gated for F4/80+ cells and examined for coexpression of CD11c (lower panels). Data from a representative experiment are shown. The percentage of CD11c+ cells within the F4/80+ ATM population is indicated for each condition. (B and C) Quantitation of CD11c+ and CD11c– ATM subpopulations in epididymal fat pads. Flow cytometry was used to assess the percentages of F4/80+CD11c+ and F4/80+CD11c– ATMs in SVF samples from ND- and HFD-fed C57BL/6 mice and HFD-fed CCR2KO mice (n = 3–4 mice per condition). Data are presented as total number of cells per mouse for each ATM subtype (B) and as cell counts normalized to cell number and fat pad weight (C). Data are presented as mean ± SD *P < 0.05 versus ND. (D) Analysis of CD11c expression in ATMs isolated from epididymal fat pads from male CCR2KO mice on a C57BL/6 background on ND or HFD. Cell isolation and flow cytometry were performed as described for A.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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