Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice

Pingping Li, Min Lu, M. T.Audrey Nguyen, Eun Ju Bae, Justin Chapman, Daorong Feng, Meredith Hawkins, Jeffrey E. Pessin, Dorothy D. Sears, Anh Khoi Nguyen, Arezou Amidi, Steven M. Watkins, Uyenthao Nguyen, Jerrold M. Olefsky

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146 Scopus citations

Abstract

Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker.Weassessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD3NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation.

Original languageEnglish (US)
Pages (from-to)15333-15345
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number20
DOIs
StatePublished - May 14 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Li, P., Lu, M., Nguyen, M. T. A., Bae, E. J., Chapman, J., Feng, D., Hawkins, M., Pessin, J. E., Sears, D. D., Nguyen, A. K., Amidi, A., Watkins, S. M., Nguyen, U., & Olefsky, J. M. (2010). Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. Journal of Biological Chemistry, 285(20), 15333-15345. https://doi.org/10.1074/jbc.M110.100263