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Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Authors :
Steven M. Watkins
Arezou Amidi
Meredith Hawkins
Dorothy D. Sears
Uyenthao Nguyen
Pingping Li
M. T. Audrey Nguyen
Jeffrey E. Pessin
Justin Chapman
Anh Khoi Nguyen
Daorong Feng
Jerrold M. Olefsky
Eun Ju Bae
Min Lu
Source :
Journal of Biological Chemistry. 285:15333-15345
Publication Year :
2010
Publisher :
Elsevier BV, 2010.

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. We assessed 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 HFD → NC 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.

Details

ISSN :
00219258
Volume :
285
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi.dedup.....08565ce76650b8a5c3ba9e180b100f9a
Full Text :
https://doi.org/10.1074/jbc.m110.100263