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.
Highlights
Macrophages are resident immune cells found in most of tissues [1]
These results indicate that diphtheria toxin (DT) injection induced macrophage depletion regardless of its activation state in LysMCre/iDTR mice
The studies related to obesity-induced tissue macrophage infiltration have demonstrated a close association of energy metabolism with immunity [3,4]
Summary
Macrophages are resident immune cells found in most of tissues [1]. Recently, their relevance with obesity-induced metabolic syndrome has been highlighted [2]. Macrophages present in non-obese conditions appear to be antiinflammatory, which play a role in maintaining tissue functions [9]. A certain population of macrophages has been shown to be induced and associated with tissue metabolism under certain pathological circumstances, it is largely unknown whether macrophages modulate systemic energy homeostasis at physiological conditions. In this regard, we depleted tissue macrophages in adult mice and found that macrophages play a role in controlling NE tissue infiltration at least partially by regulating G-CSF production, which was closely associated with alterations in food intake and body composition. Our study suggests homeostatic functions of macrophage to integrate immunity with energy metabolism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
