MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue
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Transcription factor MAFB regulates various homeostatic functions of macrophages. This study explores the role of MAFB in brown adipose tissue (BAT) thermogenesis using macrophage-specific Mafb-deficient (Mafbf/f::LysM-Cre) mice. We find that Mafb deficiency in macrophages reduces thermogenesis, energy expenditure, and sympathetic neuron (SN) density in BAT under cold conditions. This phenotype features a proinflammatory environment that is characterized by macrophage/granulocyte accumulation, increases in interleukin-6 (IL-6) production, and IL-6 trans-signaling, which lead to decreases in nerve growth factor (NGF) expression and reduction in SN density in BAT. We confirm MAFB regulation of IL-6 expression using luciferase readout driven by IL-6 promoter in RAW-264.7 macrophage cell lines. Immunohistochemistry shows clustered organization of NGF-producing cells in BAT, which are primarily TRPV1+ vascular smooth muscle cells, as additionally shown using single-cell RNA sequencing and RT-qPCR of the stromal vascular fraction. Treating Mafbf/f::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure.
Original language | English |
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Article number | 113978 |
Journal | Cell Reports |
Volume | 43 |
Issue number | 4 |
Number of pages | 19 |
ISSN | 2211-1247 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2024 The Author(s)
- BAT, brown adipose tissue thermogenesis, CP: Immunology, CP: Metabolism, interleukin-6 (IL-6), MAFB, nerve growth factor, NGF, progenitors of brown adipocytes, SN, sympathetic neuronal density, TRPV1+ vascular smooth muscle cells
Research areas
ID: 388041709