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

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 2

CD11c+ ATMs in SVF cultures and in adipose tissue from obese mice.

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CD11c+ ATMs in SVF cultures and in adipose tissue from obese mice. ...
(A) Identification of F4/80+ and CD11c+ ATMs by immunofluorescence microscopy. Epididymal fat pads from ND and HFD mice were separated into adipocyte and SVF fractions. SVF cells were plated onto glass coverslips and cultured overnight prior to fixation. Cells were stained with antibodies against F4/80 (left) and CD11c (middle) and imaged by confocal microscopy to identify surface markers to confirm the presence of CD11c+ cells only in the SVF from HFD-fed animals. Similar results were obtained for 3 independent sets of cultures. (B) Immunohistochemical localization of CD11c+ in adipose tissue. Consecutive sections from epididymal fat pads from obese C57BL/6 mice were stained with anti-F4/80 (left panels) and anti-CD11c antibodies (right panels), followed by colorimetric detection (brown). Sections were counterstained with hematoxylin (blue) and images taken at low (×200) and high magnification (×1,000). (C) In obese mice, CD11c+ cells were also detected surrounding normal-appearing adipocytes in the absence of crownlike macrophage clusters (×1,000 magnification).