MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue.

Cell reports 2024 Apr 23

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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. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Manoj Kumar Yadav, Megumi Ishida, Natalia Gogoleva, Ching-Wei Liao, Filiani Natalia Salim, Maho Kanai, Akihiro Kuno, Takuto Hayashi, Zeynab Javanfekr Shahri, Kaushalya Kulathunga, Omar Samir, Wenxin Lyu, Olivia Olivia, Evaristus C Mbanefo, Satoru Takahashi, Michito Hamada. MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue. Cell reports. 2024 Apr 23;43(4):113978