Activation of adipose tissue macrophages in obese mice does not require lymphocytes

Authors

  • James W. Behan,

    1. Division of Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Ehsan A. Ehsanipour,

    1. Division of Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Xia Sheng,

    1. Division of Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Rocky Pramanik,

    1. Division of Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Xingchao Wang,

    1. Department of Pathology, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Yao-Te Hsieh,

    1. Division of Hematology & Oncology, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Yong-Mi Kim,

    1. Division of Hematology & Oncology, Children's Hospital Los Angeles, Los Angeles, California, USA
    2. Division of Hematology & Oncology, Keck School of Medicine, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
    3. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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  • Steven D. Mittelman

    Corresponding author
    1. Division of Hematology & Oncology, Keck School of Medicine, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
    2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    3. Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    • Division of Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA
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  • Disclosure: The authors declared no conflicts of interest.

    Funding agencies: This research was sponsored by The National Cancer Institute (CA139060), The TJ Martell Foundation, and The Children's Cancer Research Fund, a California non-profit organization.

Correspondence: Steven D. Mittelman (smittelman@chla.usc.edu)

Abstract

Objective

Macrophages which infiltrate adipose tissue and secrete proinflammatory cytokines may be responsible for obesity-induced insulin resistance. However, the reason why macrophages migrate into adipose tissue and become activated remains unknown though some studies suggest that this may be regulated by T and B lymphocytes. In this study, it has been tested whether T and B lymphocytes and natural killer (NK) cells were necessary for the obesity-induced activation of macrophages in adipose tissue.

Design and Methods

NOD/SCID/IL2-receptor gamma-chain knockout (NSG) mice, which lack mature T and B lymphocytes and NK cells, were made obese by selectively reducing litters and weaning onto a high-fat diet. Mice were then maintained on the diet for 10–11 weeks.

Results

Adipose tissue from obese NSG mice had more activated macrophages than nonobese mice. These macrophages were found in “crown-like structures” surrounding adipocytes, and expressed higher levels of the inflammatory cytokine TNF-α. However, obesity did not impair glucose tolerance in the NSG mice.

Conclusions

These studies demonstrated that T and B lymphocytes and NK cells are not necessary for adipose tissue macrophage activation in obese mice. T and B lymphocytes and/or NK cells may be necessary for the development of obesity-induced impaired glucose tolerance.

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