title: IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge.
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.
authors.affiliation: Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Spadaro
authors.affiliation: Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Camell
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bosurgi
authors.affiliation: Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Nguyen
authors.affiliation: Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Youm
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Carla V
authors.initials: CV
authors.lastname: Rothlin
authors.affiliation: Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: vishwa.dixit@yale.edu.
authors.forename: Vishwa Deep
authors.initials: VD
authors.lastname: Dixit
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D059305:Diet, High-Fat; D007333:Insulin Resistance / Q000235:genetics* / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000472:pathogenicity; D010587:Phagocytosis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
chemical_list: C519530:insulin-like growth factor-1, mouse; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I
keywords: UCP-1; catecholamines; immunometabolism; inflammation; neutrophils; tyrosine hydroxylase