title: Macrophage depletion disrupts immune balance and energy homeostasis.
abstract: Increased macrophage infiltration in tissues including white adipose tissue and skeletal muscle has been recognized as a pro-inflammatory factor that impairs insulin sensitivity in obesity. However, the relationship between tissue macrophages and energy metabolism under non-obese physiological conditions is not clear. To study a homeostatic role of macrophages in energy homeostasis, we depleted tissue macrophages in adult mice through conditional expression of diphtheria toxin (DT) receptor and DT-induced apoptosis. Macrophage depletion robustly reduced body fat mass due to reduced energy intake. These phenotypes were reversed after macrophage recovery. As a potential mechanism, severe hypothalamic and systemic inflammation was induced by neutrophil (NE) infiltration in the absence of macrophages. In addition, macrophage depletion dramatically increased circulating granulocyte colony-stimulating factor (G-CSF) which is indispensable for NE production and tissue infiltration. Our in vitro study further revealed that macrophages directly suppress G-CSF gene expression. Therefore, our study indicates that macrophages may play a critical role in integrating immune balance and energy homeostasis under physiological conditions.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Brice
authors.initials: B
authors.lastname: Kinney
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Feng
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shao
mesh_terms: D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D002149:Energy Intake; D004734:Energy Metabolism; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007109:Immunity; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050796:STAT3 Transcription Factor; D016179:Granulocyte Colony-Stimulating Factor