IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

Olga Spadaro, Christina D. Camell, Lidia Bosurgi, Kim Y. Nguyen, Yun Hee Youm, Carla V. Rothlin, Vishwa Deep Dixit

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42 Scopus citations

Abstract

In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R knockout (MIKO) mice revealed a reduction in transcripts associated with M2-like macrophage activation. Furthermore, the MIKO mice infected with helminth Nippostrongylus brasiliensis displayed delayed resolution from infection with normal insulin sensitivity. Surprisingly, cold challenge did not trigger an overt M2-like state and failed to induce tyrosine hydroxylase expression in adipose tissue macrophages of control or MIKO mice. These results show that IGF1 signaling shapes the macrophage-activation phenotype.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalCell reports
Volume19
Issue number2
DOIs
StatePublished - Apr 11 2017

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Keywords

  • UCP-1
  • catecholamines
  • immunometabolism
  • inflammation
  • neutrophils
  • tyrosine hydroxylase

Cite this

Spadaro, O., Camell, C. D., Bosurgi, L., Nguyen, K. Y., Youm, Y. H., Rothlin, C. V., & Dixit, V. D. (2017). IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge. Cell reports, 19(2), 225-234. https://doi.org/10.1016/j.celrep.2017.03.046