Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice

  1. Shiho Fujisaka1,
  2. Isao Usui1,
  3. Agussalim Bukhari1,
  4. Masashi Ikutani2,
  5. Takeshi Oya3,
  6. Yukiko Kanatani1,
  7. Koichi Tsuneyama4,
  8. Yoshinori Nagai2,
  9. Kiyoshi Takatsu2,
  10. Masaharu Urakaze1,
  11. Masashi Kobayashi5 and
  12. Kazuyuki Tobe1
  1. 1First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, Tokyo, Japan;
  2. 2Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, Tokyo, Japan;
  3. 3Department of Pathology, University of Toyama, Toyama, Japan;
  4. 4Department of Diagnostic Pathology, University of Toyama, Toyama, Japan;
  5. 5University Hospital, University of Toyama, Toyama, Japan.
  1. Corresponding author: Isao Usui, isaousui-tym{at}


OBJECTIVE To characterize the phenotypic changes of adipose tissue macrophages (ATMs) under different conditions of insulin sensitivity.

RESEARCH DESIGN AND METHODS The number and the expressions of marker genes for M1 and M2 macrophages from mouse epididymal fat tissue were analyzed using flow cytometry after the mice had been subjected to a high-fat diet (HFD) and pioglitazone treatment.

RESULTS Most of the CD11c-positive M1 macrophages and the CD206-positive M2 macrophages in the epididymal fat tissue were clearly separated using flow cytometry. The M1 and M2 macrophages exhibited completely different gene expression patterns. Not only the numbers of M1 ATMs and the expression of M1 marker genes, such as tumor necrosis factor-α and monocyte chemoattractant protein-1, but also the M1-to-M2 ratio were increased by an HFD and decreased by subsequent pioglitazone treatment, suggesting the correlation with whole-body insulin sensitivity. We also found that the increased number of M2 ATMs after an HFD was associated with the upregulated expression of interleukin (IL)-10, an anti-inflammatory Th2 cytokine, in the adipocyte fraction as well as in adipose tissue. The systemic overexpression of IL-10 by an adenovirus vector increased the expression of M2 markers in adipose tissue.

CONCLUSIONS M1 and M2 ATMs constitute different subsets of macrophages. Insulin resistance is associated with both the number of M1 macrophages and the M1-to-M2 ratio. The increased expression of IL-10 after an HFD might be involved in the increased recruitment of M2 macrophages.


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    • Received October 24, 2008.
    • Accepted July 28, 2009.
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  1. Diabetes vol. 58 no. 11 2574-2582
  1. All Versions of this Article:
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